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

References

• Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med 2010;362:529–35
   PubMed Web of Science ®Google Scholar
• Romero R, Espinoza J, Kusanovic JP, et al. The preterm parturition syndrome. BJOG 2006;113:17–42
   PubMed Web of Science ®Google Scholar
• Iams JD, Romero R, Culhane JF, Goldenberg RL. Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet 2008;371:164–75
   PubMed Web of Science ®Google Scholar
• Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: when? Where? Why? Lancet 2005;365:891–900
   PubMed Web of Science ®Google Scholar
• Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:75–84
   PubMed Web of Science ®Google Scholar
• Bobitt JR, Ledger WJ. Unrecognized amnionitis and prematurity: a preliminary report. J Reprod Med 1977;19:8–12
   PubMed Web of Science ®Google Scholar
• Bobitt JR, Ledger WJ. Amniotic fluid analysis. Its role in maternal neonatal infection. Obstet Gynecol 1978;51:56–62
   PubMed Web of Science ®Google Scholar
• Miller JM, Jr Pupkin MJ, Hill GB. Bacterial colonization of amniotic fluid from intact fetal membranes. Am J Obstet Gynecol 1980;136:796–804
   PubMed Web of Science ®Google Scholar
• Wallace RL, Herrick CN. Amniocentesis in the evaluation of premature labor. Obstet Gynecol 1981;57:483–6
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Wahbeh CJ, Hill GB, Eden RD, Gall SA. Intra-amniotic bacterial colonization in premature labor. Am J Obstet Gynecol 1984;148:739–43
   PubMed Web of Science ®Google Scholar
• Gravett MG, Hummel D, Eschenbach DA, Holmes KK. Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol 1986;67:229–37
   PubMed Web of Science ®Google Scholar
• Romero R, Mazor M, Wu YK, et al. Infection in the pathogenesis of preterm labor. Semin Perinatol 1988;12:262–79
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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;161:813–6
   PubMed Web of Science ®Google Scholar
• Gibbs RS, Romero R, Hillier SL, et al. A review of premature birth and subclinical infection. Am J Obstet Gynecol 1992;166:1515–28
   PubMed Web of Science ®Google Scholar
• Watts DH, Krohn MA, Hillier SL, Eschenbach DA. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol 1992;79:351–7
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Romero R, Gomez R, Chaiworapongsa T, et al. The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol 2001;15:41–56
   PubMed Web of Science ®Google Scholar
• Gray DJ, Robinson HB, Malone J, Thomson RB Jr. Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum. Prenat Diagn 1992;12:111–7
   PubMed Web of Science ®Google Scholar
• 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 e371–5
   Web of Science ®Google Scholar
• 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: Elsevier; 2009:521–43
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Garite TJ, Freeman RK, Linzey EM, Braly P. The use of amniocentesis in patients with premature rupture of membranes. Obstet Gynecol 1979;54:226-30
   PubMed Web of Science ®Google Scholar
• Miller JM, Jr Hill GB, Welt SI, Pupkin MJ. Bacterial colonization of amniotic fluid in the presence of ruptured membranes. Am J Obstet Gynecol 1980;137:451–8
   PubMed Web of Science ®Google Scholar
• Cotton DB, Hill LM, Strassner HT, et al. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol 1984;63:38–43
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Gomez R, Romero R, Edwin SS, David C. Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intraamniotic infection. Infect Dis Clin North Am 1997;11:135–76
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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;34:13–19
   PubMed Web of Science ®Google Scholar
• 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 e431–8
   Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Mays JK, Figueroa R, Shah J, et al. Amniocentesis for selection before rescue cerclage. Obstet Gynecol 2000;95:652–5
   PubMed Web of Science ®Google Scholar
• 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 e631–8
   Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Romero R, Shamma F, Avila C, et al. Infection and labor. VI. Prevalence, microbiology, and clinical significance of intraamniotic infection in twin gestations with preterm labor. Am J Obstet Gynecol 1990;163:757–61
   PubMed Web of Science ®Google Scholar
• Mazor M, Hershkovitz R, Ghezzi F, et al. Intraamniotic infection in patients with preterm labor and twin pregnancies. Acta Obstet Gynecol Scand 1996;75:624–7
   PubMed Web of Science ®Google Scholar
• Yoon BH, Park KH, Koo JN, et al. Intramniotic infection of twin pregnancies with preterm labor. Am J Obstet Gynecol 1997;176:S35
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Thorp JM, Jr Katz VL, Fowler LJ, et al. Fetal death from chlamydial infection across intact amniotic membranes. Am J Obstet Gynecol 1989;161:1245–6
   PubMed Web of Science ®Google Scholar
• Goldenberg RL, Thompson C. The infectious origins of stillbirth. Am J Obstet Gynecol 2003;189:861–73
   PubMed Web of Science ®Google Scholar
• Blackwell S, Romero R, Chaiworapongsa T, et al. Maternal and fetal inflammatory responses in unexplained fetal death. J Matern Fetal Neonatal Med 2003;14:151–7
   PubMedGoogle Scholar
• Horvath B, Yang M, Manning FA. Intrauterine fetal death caused by Haemophilus influenzae infection: a case report. J Reprod Med 2008;53:55–6
   PubMed Web of Science ®Google Scholar
• Vigliani M. Chorioamnionitis and intrauterine fetal death after second-trimester amniocentesis. Fetal Diagn Ther 2009;26:216–8
   PubMed Web of Science ®Google Scholar
• Cassell GH, Davis RO, Waites KB, et al. Isolation of Mycoplasma hominis and Ureaplasma urealyticum from amniotic fluid at 16–20 weeks of gestation: potential effect on outcome of pregnancy. Sex Transm Dis 1983;10:294–302
   PubMed Web of Science ®Google Scholar
• Horowitz S, Mazor M, Romero R, et al. Infection of the amniotic cavity with Ureaplasma urealyticum in the midtrimester of pregnancy. J Reprod Med 1995;40:375–9
   PubMed Web of Science ®Google Scholar
• Berg TG, Philpot KL, Welsh MS, et al. Ureaplasma/Mycoplasma-infected amniotic fluid: pregnancy outcome in treated and nontreated patients. J Perinatol 1999;19:275–7
   PubMedGoogle Scholar
• Nguyen DP, Gerber S, Hohlfeld P, et al. Mycoplasma hominis in mid-trimester amniotic fluid: relation to pregnancy outcome. J Perinat Med 2004;32:323–6
   PubMed Web of Science ®Google Scholar
• Rallu F, Morency AM, Laferriere C, Bujold E. Invasion of the amniotic cavity by an uncultured bacterium, a Gram-positive coccus. J Matern Fetal Neonatal Med 2007;20:185–7
   PubMed Web of Science ®Google Scholar
• Rodriguez N, Fernandez C, Zamora Y, et al. Detection of Ureaplasma urealyticum and Ureaplasma parvum in amniotic fluid: association with pregnancy outcomes. J Matern Fetal Neonatal Med 2011;24:47–50
   PubMed Web of Science ®Google Scholar
• Prevedourakis CN, Strigou-Charalabis E, Kaskarelis DB. Bacterial invasion of amniotic cavity during pregnancy and labor. Obstet Gynecol 1971;37:459–61
   PubMed Web of Science ®Google Scholar
• Goldstein I, Zimmer EZ, Merzbach D, et al. Intraamniotic infection in the very early phase of the second trimester. Am J Obstet Gynecol 1990;163:1261–3
   PubMed Web of Science ®Google Scholar
• Romero R, Mazor M, Morrotti R, et al. Infection and labor. VII. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term. Am J Obstet Gynecol 1992;166:129–33
   PubMed Web of Science ®Google Scholar
• Romero R, Nores J, Mazor M, et al. Microbial invasion of the amniotic cavity during term labor. Prevalence and clinical significance. J Reprod Med. 1993;38:543–8
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev 2002;8:3–13
   PubMedGoogle Scholar
• Maxwell NC, Davies PL, Kotecha S. Antenatal infection and inflammation: what's new? Curr Opin Infect Dis 2006;19:253–8
   PubMed Web of Science ®Google Scholar
• Hameed C, Tejani N, Verma UL, Archbald F. Silent chorioamnionitis as a cause of preterm labor refractory to tocolytic therapy. Am J Obstet Gynecol 1984;149:726–30
   PubMed Web of Science ®Google Scholar
• Duff P, Kopelman JN. Subclinical intra-amniotic infection in asymptomatic patients with refractory preterm labor. Obstet Gynecol 1987;69:756–9
   PubMed Web of Science ®Google Scholar
• Blackwell SC, Berry SM. Role of amniocentesis for the diagnosis of subclinical intra-amniotic infection in preterm premature rupture of the membranes. Curr Opin Obstet Gynecol 1999;11:541–7
   PubMed Web of Science ®Google Scholar
• Chaiworapongsa T, Romero R, Berry SM, et al. The role of granulocyte colony-stimulating factor in the neutrophilia observed in the fetal inflammatory response syndrome. J Perinat Med 2011;39:653–66
   PubMed Web of Science ®Google Scholar
• Savasan ZA, Chaiworapongsa T, Romero R, et al. Interleukin-19 in fetal systemic inflammation. J Matern Fetal Neonatal Med 2012;25:995–1005
   PubMed Web of Science ®Google Scholar
• Stampalija T, Romero R, Korzeniewski SJ, et al. Soluble ST2 in the fetal inflammatory response syndrome: in vivo evidence of activation of the anti-inflammatory limb of the immune response. J Matern Fetal Neonatal Med 2013;26(14):1384--93
   PubMed Web of Science ®Google Scholar
• Gomez R, Romero R, Ghezzi F, et al. The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998;179:194–202
   PubMed Web of Science ®Google Scholar
• Yoon BH, Romero R, Kim KS, et al. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1999;181:773–9
   PubMed Web of Science ®Google Scholar
• Gravett MG, Hitti J, Hess DL, Eschenbach DA. Intrauterine infection and preterm delivery: evidence for activation of the fetal hypothalamic-pituitary-adrenal axis. Am J Obstet Gynecol 2000;182:1404–13
   PubMed Web of Science ®Google Scholar
• Dammann O, Phillips TM, Allred EN, et al. Mediators of fetal inflammation in extremely low gestational age newborns. Cytokine 2001;13:234–9
   PubMed Web of Science ®Google Scholar
• Witt A, Berger A, Gruber CJ, et al. IL-8 concentrations in maternal serum, amniotic fluid and cord blood in relation to different pathogens within the amniotic cavity. J Perinat Med 2005;33:22–6
   PubMed Web of Science ®Google Scholar
• Gotsch F, Romero R, Kusanovic JP, et al. The fetal inflammatory response syndrome. Clin Obstet Gynecol 2007;50:652–83
   PubMed Web of Science ®Google Scholar
• Madsen-Bouterse SA, Romero R, Tarca AL, et al. The transcriptome of the fetal inflammatory response syndrome. Am J Reprod Immunol 2010;63:73–92
   PubMed Web of Science ®Google Scholar
• Kacerovsky M, Cobo T, Andrys C, et al. The fetal inflammatory response in subgroups of women with preterm prelabor rupture of the membranes. J Matern Fetal Neonatal Med 2013;26:795–801
   PubMed Web of Science ®Google Scholar
• Kramer BW, Moss TJ, Willet KE, et al. Dose and time response after intraamniotic endotoxin in preterm lambs. Am J Respir Crit Care Med 2001;164:982–8
   PubMed Web of Science ®Google Scholar
• Moss TJ, Nitsos I, Ikegami M, et al. Experimental intrauterine Ureaplasma infection in sheep. Am J Obstet Gynecol 2005;192:1179–86
   PubMed Web of Science ®Google Scholar
• Goldenberg RL, Andrews WW, Goepfert AR, et al. The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol 2008;198:43 e41–5
   Web of Science ®Google Scholar
• Moss TJ, Knox CL, Kallapur SG, et al. Experimental amniotic fluid infection in sheep: effects of Ureaplasma parvum serovars 3 and 6 on preterm or term fetal sheep. Am J Obstet Gynecol 2008;198:122 e121–8
   Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• Leviton A, Hecht JL, Allred EN, et al. Persistence after birth of systemic inflammation associated with umbilical cord inflammation. J Reprod Immunol 2011;90:235–43
   PubMed Web of Science ®Google Scholar
• Carroll SG, Nicolaides KH. Fetal haematological response to intra-uterine infection in preterm prelabour amniorrhexis. Fetal Diagn Ther 1995;10:279–85
   PubMed Web of Science ®Google Scholar
• Sampson JE, Theve RP, Blatman RN, et al. Fetal origin of amniotic fluid polymorphonuclear leukocytes. Am J Obstet Gynecol 1997;176:77–81
   PubMed Web of Science ®Google Scholar
• Kramer BW, Kallapur SG, Moss TJ, et al. Intra-amniotic LPS modulation of TLR signaling in lung and blood monocytes of fetal sheep. Innate Immun 2009;15:101–7
   PubMed Web of Science ®Google Scholar
• Romero R, Savasan ZA, Chaiworapongsa T, et al. Hematologic profile of the fetus with systemic inflammatory response syndrome. J Perinat Med 2011;40:19–32
   PubMed Web of Science ®Google Scholar
• Yoon BH, Romero R, Jun JK, et al. An increase in fetal plasma cortisol but not dehydroepiandrosterone sulfate is followed by the onset of preterm labor in patients with preterm premature rupture of the membranes. Am J Obstet Gynecol 1998;179:1107–14
   PubMed Web of Science ®Google Scholar
• Kim YM, Romero R, Chaiworapongsa T, et al. Dermatitis as a component of the fetal inflammatory response syndrome is associated with activation of Toll-like receptors in epidermal keratinocytes. Histopathology 2006;49:506–14
   PubMed Web of Science ®Google Scholar
• Kemp MW, Saito M, Nitsos I, et al. Exposure to in utero lipopolysaccharide induces inflammation in the fetal ovine skin. Reprod Sci 2011;18:88–98
   PubMed Web of Science ®Google Scholar
• Romero R, Espinoza J, Goncalves LF, et al. Fetal cardiac dysfunction in preterm premature rupture of membranes. J Matern Fetal Neonatal Med 2004;16:146–57
   PubMedGoogle Scholar
• Di Naro E, Cromi A, Ghezzi F, et al. Fetal thymic involution: a sonographic marker of the fetal inflammatory response syndrome. Am J Obstet Gynecol 2006;194:153–9
   PubMed Web of Science ®Google Scholar
• Murphy DJ, Sellers S, MacKenzie IZ, et al. Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies. Lancet 1995;346:1449–54
   PubMed Web of Science ®Google Scholar
• Watterberg KL, Demers LM, Scott SM, Murphy S. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996;97:210–5
   PubMed Web of Science ®Google Scholar
• Jobe AH, Newnham JP, Willet KE, et al. Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs. Am J Obstet Gynecol 2000;182:401–8
   PubMed Web of Science ®Google Scholar
• Speer CP. New insights into the pathogenesis of pulmonary inflammation in preterm infants. Biol Neonate 2001;79:205–9
   PubMedGoogle Scholar
• Willet KE, Kramer BW, Kallapur SG, et al. Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung. Am J Physiol Lung Cell Mol Physiol 2002;282:L411–20
   PubMed Web of Science ®Google Scholar
• Speer CP. Inflammation and bronchopulmonary dysplasia. Semin Neonatol 2003;8:29–38
   PubMedGoogle Scholar
• Jobe AH, Ikegami M. Antenatal infection/inflammation and postnatal lung maturation and injury. Respir Res 2001;2:27–32
   PubMed Web of Science ®Google Scholar
• Jobe AH. Antenatal associations with lung maturation and infection. J Perinatol 2005;25:S31–5
   PubMedGoogle Scholar
• Kramer BW, Kallapur S, Newnham J, Jobe AH. Prenatal inflammation and lung development. Semin Fetal Neonatal Med 2009;14:2–7
   PubMed Web of Science ®Google Scholar
• Yoon BH, Romero R, Yang SH, et al. Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia. Am J Obstet Gynecol 1996;174:1433–40
   PubMed Web of Science ®Google Scholar
• Yoon BH, Jun JK, Romero R, et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol 1997;177:19–26
   PubMed Web of Science ®Google Scholar
• Yoon BH, Romero R, Kim CJ, et al. High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia. Am J Obstet Gynecol 1997;177:406–11
   PubMed Web of Science ®Google Scholar
• Dammann O, Leviton A. Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant. Semin Pediatr Neurol 1998;5:190–201
   PubMedGoogle Scholar
• Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997;278:207–11
   PubMed Web of Science ®Google Scholar
• Leviton A, Paneth N, Reuss ML, et al. Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators. Pediatr Res 1999;46:566–75
   PubMed Web of Science ®Google Scholar
• Moon JB, Kim JC, Yoon BH, et al. Amniotic fluid matrix metalloproteinase-8 and the development of cerebral palsy. J Perinat Med 2002;30:301–6
   PubMed Web of Science ®Google Scholar
• Wharton KN, Pinar H, Stonestreet BS, et al. Severe umbilical cord inflammation-a predictor of periventricular leukomalacia in very low birth weight infants. Early Hum Dev 2004;77:77–87
   PubMed Web of Science ®Google Scholar
• Hagberg H, Mallard C. Effect of inflammation on central nervous system development and vulnerability. Curr Opin Neurol 2005;18:117–23
   PubMed Web of Science ®Google Scholar
• Romero R, Gomez R, Ghezzi F, et al. A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol 1998;179:186–93
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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;159:114–9
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Kiltz RJ, Burke MS, Porreco RP. Amniotic fluid glucose concentration as a marker for intra-amniotic infection. Obstet Gynecol 1991;78:619–22
   PubMed Web of Science ®Google Scholar
• Kirshon B, Rosenfeld B, Mari G, Belfort M. Amniotic fluid glucose and intraamniotic infection. Am J Obstet Gynecol 1991;164:818–20
   PubMed Web of Science ®Google Scholar
• Gonen R. Amniotic fluid glucose and intraamniotic infection: sensitivity, specificity, and predictive values. Am J Obstet Gynecol 1992;166:1863–4
   PubMed Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• 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 370–361
   PubMed Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Romero R, Kadar N, Hobbins JC, Duff GW. Infection and labor: the detection of endotoxin in amniotic fluid. Am J Obstet Gynecol 1987;157:815–9
   PubMed Web of Science ®Google Scholar
• Cox SM, MacDonald PC, Casey ML. Assay of bacterial endotoxin (lipopolysaccharide) in human amniotic fluid: potential usefulness in diagnosis and management of preterm labor. Am J Obstet Gynecol 1988;159:99–106
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Romero R, Emamian M, Quintero R, et al. Diagnosis of intra-amniotic infection: the acridine orange stain. Am J Perinatol 1989;6:41–5
   PubMed Web of Science ®Google Scholar
• Hoskins IA, Johnson TR, Winkel CA. Leukocyte esterase activity in human amniotic fluid for the rapid detection of chorioamnionitis. Am J Obstet Gynecol 1987;157:730–2
   PubMed Web of Science ®Google Scholar
• Gravett MG, Eschenbach DA, Speigel-Brown CA, Holmes KK. Rapid diagnosis of amniotic-fluid infection by gas-liquid chromatography. N Engl J Med 1982;306:725–8
   PubMed Web of Science ®Google Scholar
• Romero R, Scharf K, Mazor M, et al. The clinical value of gas-liquid chromatography in the detection of intra-amniotic microbial invasion. Obstet Gynecol 1988;72:44–50
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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 220–203
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Negishi H, Yamada H, Mikuni M, et al. Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery. J Perinat Med 1996;24:633–9
   PubMed Web of Science ®Google Scholar
• Hsu CD, Meaddough E, Hong SF, et al. Elevated amniotic fluid nitric oxide metabolites and interleukin-6 in intra-amniotic infection. J Soc Gynecol Investig 1998;5:21–4
   PubMedGoogle Scholar
• Kara M, Ozden S, Arioglu P, Cetin A. The significance of amniotic fluid interleukin-6 levels in preterm labour. Aust N Z J Obstet Gynaecol 1998;38:403–6
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Hsu CD, Meaddough E, Aversa K, et al. Elevated amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 in intra-amniotic infection. Am J Obstet Gynecol 1998;179:1267–70
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Massaro G, Scaravilli G, Simeone S, et al. Interleukin-6 and Mycoplasma hominis as markers of preterm birth and related brain damage: our experience. J Matern Fetal Neonatal Med 2009;22:1063–7
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Romero R, Durum SK, Dinarello CA. Interleukin-1: A signal for the initiation of labor in chorioamnionitis. Society for Gynecologic Investigation (33rd Annual Meeting). Toronto, Ontario; 1986, p. 71
   Google Scholar
• Romero R, Wu YK, Brody DT, et al. Human decidua: a source of interleukin-1. Obstet Gynecol 1989;73:31–4
   PubMed Web of Science ®Google Scholar
• Romero R, Parvizi ST, Oyarzun E, et al. Amniotic fluid interleukin-1 in spontaneous labor at term. J Reprod Med 1990;35:235–8
   PubMed Web of Science ®Google Scholar
• Liechty KW, Koenig JM, Mitchell MD, et al. Production of interleukin-6 by fetal and maternal cells in vivo during intraamniotic infection and in vitro after stimulation with interleukin-1. Pediatr Res 1991;29:1–4
   PubMed Web of Science ®Google Scholar
• McDuffie RS, Jr Sherman MP, Gibbs RS. Amniotic fluid tumor necrosis factor-alpha and interleukin-1 in a rabbit model of bacterially induced preterm pregnancy loss. Am J Obstet Gynecol 1992;167:1583–8
   PubMed Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• Casey ML, Cox SM, Beutler B, et al. Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor. J Clin Invest 1989;83:430–6
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Romero R, Mazor M, Sepulveda W, et al. Tumor necrosis factor in preterm and term labor. Am J Obstet Gynecol 1992;166:1576–87
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Laham N, Brennecke SP, Bendtzen K, Rice GE. Tumour necrosis factor alpha during human pregnancy and labour: maternal plasma and amniotic fluid concentrations and release from intrauterine tissues. Eur J Endocrinol 1994;131:607–14
   PubMed Web of Science ®Google Scholar
• Laham N, Van Dunne F, Abraham LJ, et al. Tumor necrosis factor-beta in human pregnancy and labor. J Reprod Immunol 1997;33:53–69
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• MacDonald PC, Koga S, Casey ML. Decidual activation in parturition: examination of amniotic fluid for mediators of the inflammatory response. Ann N Y Acad Sci 1991;622:315–30
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Saito S, Kasahara T, Kato Y, et al. Elevation of amniotic fluid interleukin 6 (IL-6), IL-8 and granulocyte colony stimulating factor (G-CSF) in term and preterm parturition. Cytokine 1993;5:81–8
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Dudley DJ, Hunter C, Varner MW, Mitchell MD. Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis. Am J Perinatol 1996;13:443–7
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Athayde N, Romero R, Maymon E, et al. A role for the novel cytokine RANTES in pregnancy and parturition. Am J Obstet Gynecol 1999;181:989–94
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Keelan JA, Yang J, Romero RJ, et al. Epithelial cell-derived neutrophil-activating peptide-78 is present in fetal membranes and amniotic fluid at increased concentrations with intra-amniotic infection and preterm delivery. Biol Reprod 2004;70:253–9
   PubMed Web of Science ®Google Scholar
• Chaiworapongsa T, Romero R, Espinoza J, et al. Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity. J Matern Fetal Neonatal Med 2005;18:405–16
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Yoon BH, Oh SY, Romero R, et al. An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery. Am J Obstet Gynecol 2001;185:1162–7
   PubMed Web of Science ®Google Scholar
• Angus SR, Segel SY, Hsu CD, et al. Amniotic fluid matrix metalloproteinase-8 indicates intra-amniotic infection. Am J Obstet Gynecol 2001;185:1232–8
   PubMed Web of Science ®Google Scholar
• Biggio JR, Jr Ramsey PS, Cliver SP, et al. Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes. Am J Obstet Gynecol 2005;192:109–13
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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 e291–5
   Web of Science ®Google Scholar
• Buhimschi IA, Christner R, Buhimschi CS, et al. Proteomic analysis of preterm parturion: a novel method of identifying the patient at risk of impending preterm delivery. Am J Obstet Gynecol 2003;187:S55
   Google Scholar
• Buhimschi IA, Christner R, Buhimschi CS. Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation. BJOG 2005;112:173–81
   PubMed Web of Science ®Google Scholar
• Buhimschi CS, Bhandari V, Hamar BD, et al. Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis. PLoS Med 2007;4:e18
   PubMed Web of Science ®Google Scholar
• Green NS, Damus K, Simpson JL, et al. Research agenda for preterm birth: recommendations from the March of Dimes. Am J Obstet Gynecol 2005;193:626–35
   PubMed Web of Science ®Google Scholar
• Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet 2008;371:261–9
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Armer TL, Duff P. Intraamniotic infection in patients with intact membranes and preterm labor. Obstet Gynecol Surv 1991;46:589–93
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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:S148–53
   Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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;179:1115–9
   PubMed Web of Science ®Google Scholar
• Bearfield C, Davenport ES, Sivapathasundaram V, Allaker RP. Possible association between amniotic fluid micro-organism infection and microflora in the mouth. BJOG 2002;109:527–33
   PubMed Web of Science ®Google Scholar
• Gerber S, Vial Y, Hohlfeld P, Witkin SS. 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Yi J, Yoon BH, Kim EC. Detection and biovar discrimination of Ureaplasma urealyticum by real-time PCR. Mol Cell Probes 2005;19:255–60
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• De Felice C, De Capua B, Costantini D, et al. Recurrent otitis media with effusion in preterm infants with histologic chorioamnionitis–a 3 years follow-up study. Early Hum Dev 2008;84:667–71
   PubMed Web of Science ®Google Scholar
• Aziz N, Cheng YW, Caughey AB. Neonatal outcomes in the setting of preterm premature rupture of membranes complicated by chorioamnionitis. J Matern Fetal Neonatal Med 2009;22:780–4
   PubMed Web of Science ®Google Scholar
• Newton ER. Chorioamnionitis and intraamniotic infection. Clin Obstet Gynecol 1993;36:795–808
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Lahra MM, Beeby PJ, Jeffery HE. Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics 2009;123:1314–9
   PubMed Web of Science ®Google Scholar
• Kallapur SG, Kramer BW, Jobe AH. Ureaplasma and BPD. Semin Perinatol 2013;37:94–101
   PubMed Web of Science ®Google Scholar
• Gibbs RS, Duff P. Progress in pathogenesis and management of clinical intraamniotic infection. Am J Obstet Gynecol 1991;164:1317–26
   PubMed Web of Science ®Google Scholar
• Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res 1997;42:1–8
   PubMed Web of Science ®Google Scholar
• O'Shea TM, Klinepeter KL, Meis PJ, Dillard RG. Intrauterine infection and the risk of cerebral palsy in very low-birthweight infants. Paediatr Perinat Epidemiol 1998;12:72–83
   PubMed Web of Science ®Google Scholar
• Wu YW, Colford JM Jr. Chorioamnionitis as a risk factor for cerebral palsy: A meta-analysis. JAMA 2000;284:1417–24
   PubMed Web of Science ®Google Scholar
• Yoon BH, Romero R, Park JS, et al. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 2000;182:675–81
   PubMed Web of Science ®Google Scholar
• Dammann O, Kuban KC, Leviton A. Perinatal infection, fetal inflammatory response, white matter damage, and cognitive limitations in children born preterm. Ment Retard Dev Disabil Res Rev 2002;8:46–50
   PubMedGoogle Scholar
• Yoon BH, Park CW, Chaiworapongsa T. Intrauterine infection and the development of cerebral palsy. BJOG 2003;110:124–7
   PubMed Web of Science ®Google Scholar
• Grether JK, Nelson KB, Walsh E, et al. Intrauterine exposure to infection and risk of cerebral palsy in very preterm infants. Arch Pediatr Adolesc Med 2003;157:26–32
   PubMed Web of Science ®Google Scholar
• Elovitz MA, Mrinalini C, Sammel MD. Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth. Pediatr Res 2006;59:50–5
   PubMed Web of Science ®Google Scholar
• Berger A, Witt A, Haiden N, et al. Intrauterine infection with Ureaplasma species is associated with adverse neuromotor outcome at 1 and 2 years adjusted age in preterm infants. J Perinat Med 2009;37:72–8
   PubMed Web of Science ®Google Scholar
• Bracci R, Buonocore G. Chorioamnionitis: a risk factor for fetal and neonatal morbidity. Biol Neonate 2003;83:85–96
   PubMedGoogle Scholar
• Gibbs RS. Chorioamnionitis and bacterial vaginosis. Am J Obstet Gynecol 1993;169:460–2
   PubMed Web of Science ®Google Scholar
• Martinelli P, Sarno L, Maruotti GM, Paludetto R. Chorioamnionitis and prematurity: a critical review. J Matern Fetal Neonatal Med 2012;25:29–31
   PubMed Web of Science ®Google Scholar
• Keski-Nisula L, Kirkinen P, Katila ML, et al. Amniotic fluid U. urealyticum colonization: significance for maternal peripartal infections at term. Am J Perinatol 1997;14:151–6
   PubMed Web of Science ®Google Scholar
• Barton JR, Sibai BM. Severe sepsis and septic shock in pregnancy. Obstet Gynecol 2012;120:689–706
   PubMed Web of Science ®Google Scholar
• Surgers L, Valin N, Carbonne B, et al. Evolving microbiological epidemiology and high fetal mortality in 135 cases of bacteremia during pregnancy and postpartum. Eur J Clin Microbiol Infect Dis 2013;32:107–13
   PubMed Web of Science ®Google Scholar
• Plachouras N, Sotiriadis A, Dalkalitsis N, et al. Fulminant sepsis after invasive prenatal diagnosis. Obstet Gynecol 2004;104:1244–7
   PubMed Web of Science ®Google Scholar
• Fernandez-Perez ER, Salman S, Pendem S, Farmer JC. Sepsis during pregnancy. Crit Care Med 2005;33:S286–93
   Web of Science ®Google Scholar
• Hatjis CG, Swain M. Systemic tocolysis for premature labor is associated with an increased incidence of pulmonary edema in the presence of maternal infection. Am J Obstet Gynecol 1988;159:723–8
   PubMed Web of Science ®Google Scholar
• Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstet Gynecol 1988;72:823–8
   PubMed Web of Science ®Google Scholar
• Russell JF. If a job is worth doing, it is worth doing twice. Nature 2013;496:7
   PubMed Web of Science ®Google Scholar
• Jaeschke R, Guyatt G, Sackett DL. Users' guides to the medical literature. III. How to use an article about a diagnostic test. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 1994;271:389–91
   PubMed Web of Science ®Google Scholar
• Enhancing reproducibility. Nat Methods. 2013;10:367
   Google Scholar
• Shafer SL, Dexter F. Publication bias, retrospective bias, and reproducibility of significant results in observational studies. Anesth Analg 2012;114:931–2
   PubMed Web of Science ®Google Scholar
• Tzoulaki I, Liberopoulos G, Ioannidis JP. Assessment of claims of improved prediction beyond the Framingham risk score. JAMA 2009;302:2345–52
   PubMed Web of Science ®Google Scholar
• Tsilidis KK, Papatheodorou SI, Evangelou E, Ioannidis JP. Evaluation of excess statistical significance in meta-analyses of 98 biomarker associations with cancer risk. J Natl Cancer Inst 2012;104:1867–78
   PubMedGoogle Scholar
• Nierenberg AA, Feinstein AR. How to evaluate a diagnostic marker test. Lessons from the rise and fall of dexamethasone suppression test. JAMA 1988;259:1699–702
   PubMed Web of Science ®Google Scholar
• Ioannidis JP. Biomarker failures. Clin Chem 2013;59:202–4
   PubMed Web of Science ®Google Scholar
• Rajasekharan S, Bar-Or A. From bench to MS bedside: challenges translating biomarker discovery to clinical practice. J Neuroimmunol 2012;248:66–72
   PubMed Web of Science ®Google Scholar
• Coultrip LL, Lien JM, Gomez R, et al. The value of amniotic fluid interleukin-6 determination in patients with preterm labor and intact membranes in the detection of microbial invasion of the amniotic cavity. Am J Obstet Gynecol 1994;171:901–11
   PubMed Web of Science ®Google Scholar
• Aguin E, Aguin T, Cordoba M, et al. Amniotic fluid inflammation with negative culture and outcome after cervical cerclage. J Matern Fetal Neonatal Med 2012;25:1990–4
   PubMed Web of Science ®Google Scholar
• Lee J, Oh KJ, Yang HJ, et al. The importance of intra-amniotic inflammation in the subsequent development of atypical chronic lung disease. J Matern Fetal Neonatal Med 2009;22:917–23
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Combs CA, Gravett MG, Garite TJ, et al. Intraamniotic inflammation may be more important than the presence of microbes as a determinant of perinatal outcome in preterm labor. Am J Obstet Gynecol 2013;208:S44
   Web of Science ®Google Scholar
• Blackstock WP, Weir MP. Proteomics: quantitative and physical mapping of cellular proteins. Trends Biotechnol 1999;17:121–7
   PubMed Web of Science ®Google Scholar
• Banks RE, Dunn MJ, Hochstrasser DF, et al. Proteomics: new perspectives, new biomedical opportunities. Lancet 2000;356:1749–56
   PubMed Web of Science ®Google Scholar
• Klein LL, Freitag BC, Gibbs RS, et al. Detection of intra-amniotic infection in a rabbit model by proteomics-based amniotic fluid analysis. Am J Obstet Gynecol 2005;193:1302–6
   PubMed Web of Science ®Google Scholar
• Huang DJ, Nelson MR, Holzgreve W. Maldi-TOF mass spectrometry for trisomy detection. Methods Mol Biol 2008;444:123–32
   PubMedGoogle Scholar
• Gravett MG, Thomas A, Schneider KA, et al. Proteomic analysis of cervical-vaginal fluid: identification of novel biomarkers for detection of intra-amniotic infection. J Proteome Res 2007;6:89–96
   PubMed Web of Science ®Google Scholar
• Pereira L, Reddy AP, Jacob T, et al. Identification of novel protein biomarkers of preterm birth in human cervical-vaginal fluid. J Proteome Res 2007;6:1269–76
   PubMed Web of Science ®Google Scholar
• Dasari S, Pereira L, Reddy AP, et al. Comprehensive proteomic analysis of human cervical-vaginal fluid. J Proteome Res 2007;6:1258–68
   PubMed Web of Science ®Google Scholar
• Shah SJ, Yu KH, Sangar V, et al. Identification and quantification of preterm birth biomarkers in human cervicovaginal fluid by liquid chromatography/tandem mass spectrometry. J Proteome Res 2009;8:2407–17
   PubMed Web of Science ®Google Scholar
• Hitti J, Lapidus JA, Lu X, et al. Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid. Am J Obstet Gynecol 2010;203:32 e31–8
   Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Gravett MG, Novy MJ, Rosenfeld RG, et al. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA 2004;292:462–9
   PubMed Web of Science ®Google Scholar
• Michaels JE, Dasari S, Pereira L, et al. Comprehensive proteomic analysis of the human amniotic fluid proteome: gestational age-dependent changes. J Proteome Res 2007;6:1277–85
   PubMed Web of Science ®Google Scholar
• Bujold E, Romero R, Kusanovic JP, et al. Proteomic profiling of amniotic fluid in preterm labor using two-dimensional liquid separation and mass spectrometry. J Matern Fetal Neonatal Med 2008;21:697–713
   PubMed Web of Science ®Google Scholar
• Romero R, Kusanovic JP, Gotsch F, et al. Isobaric labeling and tandem mass spectrometry: a novel approach for profiling and quantifying proteins differentially expressed in amniotic fluid in preterm labor with and without intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med 2010;23:261–80
   PubMed Web of Science ®Google Scholar
• Fotopoulou C, Kyeyamwa S, Linder M, et al. Proteomic analysis of midtrimester amniotic fluid to identify novel biomarkers for preterm delivery. J Matern Fetal Neonatal Med 2012;25:2488–93
   PubMed Web of Science ®Google Scholar
• Pereira L, Reddy AP, Alexander AL, et al. Insights into the multifactorial nature of preterm birth: proteomic profiling of the maternal serum glycoproteome and maternal serum peptidome among women in preterm labor. Am J Obstet Gynecol 2010;202:555 e1–10
   Web of Science ®Google Scholar
• Esplin MS, Merrell K, Goldenberg R, et al. Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth. Am J Obstet Gynecol 2011;204:391 e391–8
   Web of Science ®Google Scholar