Original Article
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
Roberto Romero,
Jezid Miranda,
Tinnakorn Chaiworapongsa,
Piya Chaemsaithong,
Francesca Gotsch,
Zhong Dong,
Ahmed I. Ahmed,
Bo Hyun Yoon,
Sonia S. Hassan,
Chong Jai Kim,
Steven J. Korzeniewski,
Lami Yeo,
Corresponding Author
Roberto Romero
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA
Correspondence
Roberto Romero, Perinatology Research Branch, NICHD/NIH/DHHS, Wayne State University/Hutzel Women's Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA.
E-mail: [email protected]
Search for more papers by this authorJezid Miranda
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorTinnakorn Chaiworapongsa
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorPiya Chaemsaithong
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorFrancesca Gotsch
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Integrata Verona, Ostetricia Ginecologia, Azienda Ospedaliera Universitaria, Verona, Italy
Search for more papers by this authorZhong Dong
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorAhmed I. Ahmed
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorBo Hyun Yoon
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorSonia S. Hassan
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorChong Jai Kim
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Search for more papers by this authorSteven J. Korzeniewski
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorLami Yeo
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorRoberto Romero,
Jezid Miranda,
Tinnakorn Chaiworapongsa,
Piya Chaemsaithong,
Francesca Gotsch,
Zhong Dong,
Ahmed I. Ahmed,
Bo Hyun Yoon,
Sonia S. Hassan,
Chong Jai Kim,
Steven J. Korzeniewski,
Lami Yeo,
Corresponding Author
Roberto Romero
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA
Correspondence
Roberto Romero, Perinatology Research Branch, NICHD/NIH/DHHS, Wayne State University/Hutzel Women's Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA.
E-mail: [email protected]
Search for more papers by this authorJezid Miranda
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorTinnakorn Chaiworapongsa
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorPiya Chaemsaithong
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorFrancesca Gotsch
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Integrata Verona, Ostetricia Ginecologia, Azienda Ospedaliera Universitaria, Verona, Italy
Search for more papers by this authorZhong Dong
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorAhmed I. Ahmed
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorBo Hyun Yoon
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorSonia S. Hassan
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorChong Jai Kim
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Search for more papers by this authorSteven J. Korzeniewski
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorLami Yeo
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, and Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorThis work was presented, in part, as an abstract at the 14th International Symposium for Immunology of Reproduction (2013). Boston, Massachusetts, USA.
Abstract
Problem
The diagnosis of microbial invasion of the amniotic cavity (MIAC) has been traditionally performed using traditional cultivation techniques, which require growth of microorganisms in the laboratory. Shortcomings of culture methods include the time required (days) for identification of microorganisms, and that many microbes involved in the genesis of human diseases are difficult to culture. A novel technique combines broad-range real-time polymerase chain reaction with electrospray ionization time-of-flight mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses.
Method of study
AF samples obtained by transabdominal amniocentesis from 142 women with preterm labor and intact membranes (PTL) were analyzed using cultivation techniques (aerobic, anaerobic, and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF interleukin 6 (IL-6) concentration ≥ 2.6 ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined.
Results
(i) The prevalence of MIAC in patients with PTL was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; (ii) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [≥17 genome equivalents per PCR reaction well (GE/well)]; (iii) patients with positive PCR/ESI-MS (≥17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and acute histologic chorioamnionitis, a shorter interval to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) versus 32% (39/122) OR: 5.6; 95% CI: 1.4–22; (P < 0.001); 70% (7/10) versus 35% (39/112); (P = 0.04); 1 (IQR: <1–2) days versus 25 (IQR: 5–51) days; (P = 0.002), respectively]; (iv) there were no significant differences in these outcomes between patients with positive PCR/ESI-MS (≥17 GE/well) who had negative AF cultures and those with positive AF cultures; and (v) PCR/ESI-MS detected genomic material from viruses in two patients (1.4%).
Conclusion
(i) Rapid diagnosis of intra-amniotic infection is possible using PCR/ESI-MS; (ii) the combined use of biomarkers of inflammation and PCR/ESI-MS allows for the identification of specific bacteria and viruses in women with preterm labor and intra-amniotic infection; and (iii) this approach may allow for administration of timely and specific interventions to reduce morbidity attributed to infection-induced preterm birth.
References
- 1 World Health Organization: Born too soon: the global action report in preterm birth. WHO Library Cataloguing-in-Publication. Geneva, Switzerland, World Health Organization, 2012.
- 2Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE: National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012; 379: 2162–2172.
- 3Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B: Annual summary of vital statistics: 2010-2011. Pediatrics 2013; 131: 548–558.
- 4 Premature Birth. In, March of Dimes (ed). 2009.
- 5Muglia LJ, Katz M: The enigma of spontaneous preterm birth. N Engl J Med 2010; 362: 529–535.
- 6Lawn JE, Cousens S, Zupan J: 4 million neonatal deaths: when? Where? Why? Lancet 2005; 365: 891–900.
- 7Bobitt JR, Ledger WJ: Unrecognized amnionitis and prematurity: a preliminary report. J Reprod Med 1977; 19: 8–12.
- 8Bobitt JR, Ledger WJ: Amniotic fluid analysis. Its role in maternal neonatal infection. Obstet Gynecol 1978; 51: 56–62.
- 9Miller JM Jr, Pupkin MJ, Hill GB: Bacterial colonization of amniotic fluid from intact fetal membranes. Am J Obstet Gynecol 1980; 136: 796–804.
- 10Wallace RL, Herrick CN: Amniocentesis in the evaluation of premature labor. Obstet Gynecol 1981; 57: 483–486.
- 11Bobitt 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: 947–952.
- 12Wahbeh CJ, Hill GB, Eden RD, Gall SA: Intra-amniotic bacterial colonization in premature labor. Am J Obstet Gynecol 1984; 148: 739–743.
- 13Hameed 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: 726–730.
- 14Gravett MG, Hummel D, Eschenbach DA, Holmes KK: Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol 1986; 67: 229–237.
- 15Leigh J, Garite TJ: Amniocentesis and the management of premature labor. Obstet Gynecol 1986; 67: 500–506.
- 16Romero R, Emamian M, Quintero R, Wan M, Hobbins JC, Mazor M, Edberg S: The value and limitations of the Gram stain examination in the diagnosis of intraamniotic infection. Am J Obstet Gynecol 1988; 159: 114–119.
- 17Romero R, Emamian M, Wan M, Yarkoni S, McCormack W, Mazor M, Hobbins JC: The value of the leukocyte esterase test in diagnosing intra-amniotic infection. Am J Perinatol 1988; 5: 64–69.
- 18Romero R, Scharf K, Mazor M, Emamian M, Hobbins JC, Ryan JL: The clinical value of gas-liquid chromatography in the detection of intra-amniotic microbial invasion. Obstet Gynecol 1988; 72: 44–50.
- 19Romero R, Mazor M, Wu YK, Sirtori M, Oyarzun E, Mitchell MD, Hobbins JC: Infection in the pathogenesis of preterm labor. Semin Perinatol 1988; 12: 262–279.
- 20Romero R, Sirtori M, Oyarzun E, Avila C, Mazor M, Callahan R, Sabo V, Athanassiadis AP, Hobbins JC: 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: 817–824.
- 21Skoll 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: 813–816.
- 22Romero R, Jimenez C, Lohda AK, Nores J, Hanaoka S, Avila C, Callahan R, Mazor M, Hobbins JC, Diamond MP: Amniotic fluid glucose concentration: a rapid and simple method for the detection of intraamniotic infection in preterm labor. Am J Obstet Gynecol 1990; 163: 968–974.
- 23Romero R, Avila C, Santhanam U, Sehgal PB: Amniotic fluid interleukin 6 in preterm labor. Association with infection. J Clin Invest 1990; 85: 1392–1400.
- 24Romero R, Quintero R, Nores J, Avila C, Mazor M, Hanaoka S, Hagay Z, Merchant L, Hobbins JC: Amniotic fluid white blood cell count: a rapid and simple test to diagnose microbial invasion of the amniotic cavity and predict preterm delivery. Am J Obstet Gynecol 1991; 165: 821–830.
- 25Gauthier DW, Meyer WJ, Bieniarz A: Correlation of amniotic fluid glucose concentration and intraamniotic infection in patients with preterm labor or premature rupture of membranes. Am J Obstet Gynecol 1991; 165: 1105–1110.
- 26Watts 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: 351–357.
- 27Coultrip LL, Grossman JH: Evaluation of rapid diagnostic tests in the detection of microbial invasion of the amniotic cavity. Am J Obstet Gynecol 1992; 167: 1231–1242.
- 28Andrews WW, Hauth JC, Goldenberg RL, Gomez R, Romero R, Cassell GH: 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: 606–612.
- 29Yoon BH, Jun JK, Park KH, Syn HC, Gomez R, Romero R: Serum C-reactive protein, white blood cell count, and amniotic fluid white blood cell count in women with preterm premature rupture of membranes. Obstet Gynecol 1996; 88: 1034–1040.
- 30Yoon BH, Chang JW, Romero R: Isolation of Ureaplasma urealyticum from the amniotic cavity and adverse outcome in preterm labor. Obstet Gynecol 1998; 92: 77–82.
- 31Hussey MJ, Levy ES, Pombar X, Meyer P, Strassner HT: 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: 650–656.
- 32Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM: The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998; 179: 194–202.
- 33Rizzo G, Capponi A, Vlachopoulou A, Angelini E, Grassi C, Romanini C: Ultrasonographic assessment of the uterine cervix and interleukin-8 concentrations in cervical secretions predict intrauterine infection in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol 1998; 12: 86–92.
- 34Oyarzun E, Yamamoto M, Kato S, Gomez R, Lizama L, Moenne A: 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: 1115–1119.
- 35Elimian A, Figueroa R, Canterino J, Verma U, Aguero-Rosenfeld M, Tejani N: Amniotic fluid complement C3 as a marker of intra-amniotic infection. Obstet Gynecol 1998; 92: 72–76.
- 36Gonzalez-Bosquet E, Cerqueira MJ, Dominguez C, Gasser I, Bermejo B, Cabero L: 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: 155–158.
- 37Locksmith GJ, Clark P, Duff P, Schultz GS: Amniotic fluid matrix metalloproteinase-9 levels in women with preterm labor and suspected intra-amniotic infection. Obstet Gynecol 1999; 94: 1–6.
- 38Ovalle A, Martinez MA, Gomez R, Saez J, Menares I, Aspillaga C, Schwarze JE: [Premature labor with intact membranes: microbiology of the amniotic fluid and lower genital tract and its relation with maternal and neonatal outcome]. Rev Med Chil 2000; 128: 985–995.
- 39Yoon BH, Romero R, Kim M, Kim EC, Kim T, Park JS, Jun JK: Clinical implications of detection of Ureaplasma urealyticum in the amniotic cavity with the polymerase chain reaction. Am J Obstet Gynecol 2000; 183: 1130–1137.
- 40Romero R, Gomez R, Chaiworapongsa T, Conoscenti G, Kim JC, Kim YM: The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol 2001; 15(Suppl. 2): 41–56.
- 41Yoon BH, Romero R, Moon JB, Shim SS, Kim M, Kim G, Jun JK: Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol 2001; 185: 1130–1136.
- 42Jacobsson B, Mattsby-Baltzer I, Andersch B, Bokstrom H, Holst RM, Wennerholm UB, Hagberg H: Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor. Acta Obstet Gynecol Scand 2003; 82: 120–128.
- 43Romero R, Lockwood CJ: Pathogenesis of spontaneous preterm labor. In Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice, 6th edn, RK Creasy, R Resnik, J Iams (eds). Philadelphia, Elsevier, 2009, pp 521–543.
10.1016/B978-1-4160-4224-2.50031-4 Google Scholar
- 44Blanco JD, Gibbs RS, Krebs LF, Castaneda YS: The association between the absence of amniotic fluid bacterial inhibitory activity and intra-amniotic infection. Am J Obstet Gynecol 1982; 143: 749–755.
- 45Gibbs RS, Blanco JD, Hnilica VS: Inorganic phosphorus and zinc concentrations in amniotic fluid: correlation with intra-amniotic infection and bacterial inhibitory activity. Am J Obstet Gynecol 1982; 143: 163–166.
- 46Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS: Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis 1982; 145: 1–8.
- 47Blanco JD, Gibbs RS, Krebs LF: Inhibition of group B streptococci by amniotic fluid from patients with intra-amniotic infection and from control subjects. Am J Obstet Gynecol 1983; 147: 247–250.
- 48Blanco JD, Gibbs RS, Krebs LF: A controlled study of amniotic fluid immunoglobulin levels in intraamniotic infection. Obstet Gynecol 1983; 61: 450–453.
- 49Blanco JD, Gibbs RS, Malherbe H, Strickland-Cholmley M, St Clair PJ, Castaneda YS: A controlled study of genital mycoplasmas in amniotic fluid from patients with intra-amniotic infection. J Infect Dis 1983; 147: 650–653.
- 50Garite TJ, Freeman RK, Linzey EM, Braly P: The use of amniocentesis in patients with premature rupture of membranes. Obstet Gynecol 1979; 54: 226–230.
- 51Minkoff H: Prematurity: infection as an etiologic factor. Obstet Gynecol 1983; 62: 137–144.
- 52Cotton DB, Hill LM, Strassner HT, Platt LD, Ledger WJ: Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol 1984; 63: 38–43.
- 53Romero R, Quintero R, Oyarzun E, Wu YK, Sabo V, Mazor M, Hobbins JC: Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes. Am J Obstet Gynecol 1988; 159: 661–666.
- 54Romero R, Mazor M: Infection and preterm labor. Clin Obstet Gynecol 1988; 31: 553–584.
- 55Asrat T, Nageotte MP, Garite TJ, Gocke SE, Dorchester W: 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: 887–889.
- 56Dudley J, Malcolm G, Ellwood D: Amniocentesis in the management of preterm premature rupture of the membranes. Aust N Z J Obstet Gynaecol 1991; 31: 331–336.
- 57Romero R, Ghidini A, Mazor M, Behnke E: Microbial invasion of the amniotic cavity in premature rupture of membranes. Clin Obstet Gynecol 1991; 34: 769–778.
- 58Gibbs RS, Romero R, Hillier SL, Eschenbach DA, Sweet RL: A review of premature birth and subclinical infection. Am J Obstet Gynecol 1992; 166: 1515–1528.
- 59Romero R, Mazor M, Morrotti R, Avila C, Oyarzun E, Insunza A, Parra M, Behnke E, Montiel F, Cassell GH: Infection and labor. VII. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term. Am J Obstet Gynecol 1992; 166: 129–133.
- 60Romero R, Yoon BH, Mazor M, Gomez R, Gonzalez R, Diamond MP, Baumann P, Araneda H, Kenney JS, Cotton DB, Sehgal P: 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: 839–851.
- 61Romero R, Yoon BH, Mazor M, Gomez R, Diamond MP, Kenney JS, Ramirez M, Fidel PL, Sorokin Y, Cotton D, Sehgal P: 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: 805–816.
- 62Romero R, Nores J, Mazor M, Sepulveda W, Oyarzun E, Parra M, Insunza A, Montiel F, Behnke E, Cassell GH: Microbial invasion of the amniotic cavity during term labor. Prevalence and clinical significance. J Reprod Med 1993; 38: 543–548.
- 63Gomez R, Romero R, Galasso M, Behnke E, Insunza A, Cotton DB: 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: 200–210.
- 64Blackwell 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: 541–547.
- 65Jacobsson B, Mattsby-Baltzer I, Andersch B, Bokstrom H, Holst RM, Nikolaitchouk N, Wennerholm UB, Hagberg H: 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: 423–431.
- 66Broekhuizen FF, Gilman M, Hamilton PR: Amniocentesis for gram stain and culture in preterm premature rupture of the membranes. Obstet Gynecol 1985; 66: 316–321.
- 67Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD: The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998; 244: 379–386.
- 68Wing DA, Park AS, Debuque L, Millar LK: Limited clinical utility of blood and urine cultures in the treatment of acute pyelonephritis during pregnancy. Am J Obstet Gynecol 2000; 182: 1437–1440.
- 69Gilstrap LC III, Ramin SM: Urinary tract infections during pregnancy. Obstet Gynecol Clin North Am 2001; 28: 581–591.
- 70Wing DA: Pyelonephritis in pregnancy: treatment options for optimal outcomes. Drugs 2001; 61: 2087–2096.
- 71Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32: 858–873.
- 72Kumar A: Optimizing antimicrobial therapy in sepsis and septic shock. Crit Care Clin 2009; 25: 733–751, viii.
- 73Jolley JA, Wing DA: Pyelonephritis in pregnancy: an update on treatment options for optimal outcomes. Drugs 2010; 70: 1643–1655.
- 74Tam CS, O'Reilly M, Andresen D, Lingaratnam S, Kelly A, Burbury K, Turnidge J, Slavin MA, Worth LJ, Dawson L, Thursky KA: Use of empiric antimicrobial therapy in neutropenic fever. Australian Consensus Guidelines 2011 Steering Committee. Intern Med J 2011; 41: 90–101.
- 75Polin RA: Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012; 129: 1006–1015.
- 76Janeway CA Jr, Medzhitov R: Innate immune recognition. Annu Rev Immunol 2002; 20: 197–216.
- 77Medzhitov R, Janeway CA Jr: Decoding the patterns of self and nonself by the innate immune system. Science 2002; 296: 298–300.
- 78Medzhitov R: Origin and physiological roles of inflammation. Nature 2008; 454: 428–435.
- 79Medzhitov R: Inflammation 2010: new adventures of an old flame. Cell 2010; 140: 771–776.
- 80Chen GY, Nunez G: Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol 2010; 10: 826–837.
- 81Relman DA, Falkow S: Identification of uncultured microorganisms: expanding the spectrum of characterized microbial pathogens. Infect Agents Dis 1992; 1: 245–253.
- 82Relman DA: Emerging infections and newly-recognised pathogens. Neth J Med 1997; 50: 216–220.
- 83Harder TC, Hufnagel M, Zahn K, Beutel K, Schmitt HJ, Ullmann U, Rautenberg P: New LightCycler PCR for rapid and sensitive quantification of parvovirus B19 DNA guides therapeutic decision-making in relapsing infections. J Clin Microbiol 2001; 39: 4413–4419.
- 84Cheng VC, Yam WC, Hung IF, Woo PC, Lau SK, Tang BS, Yuen KY: Clinical evaluation of the polymerase chain reaction for the rapid diagnosis of tuberculosis. J Clin Pathol 2004; 57: 281–285.
- 85Yang S, Rothman RE: PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings. Lancet Infect Dis 2004; 4: 337–348.
- 86Alfa MJ, Sepehri S, De Gagne P, Helawa M, Sandhu G, Harding GK: Real-time PCR assay provides reliable assessment of intrapartum carriage of group B Streptococcus. J Clin Microbiol 2010; 48: 3095–3099.
- 87Bauer M, Reinhart K: Molecular diagnostics of sepsis–where are we today? Int J Med Microbiol 2010; 300: 411–413.
- 88Gardella C, Huang ML, Wald A, Magaret A, Selke S, Morrow R, Corey L: Rapid polymerase chain reaction assay to detect herpes simplex virus in the genital tract of women in labor. Obstet Gynecol 2010; 115: 1209–1216.
- 89Blanchard A, Hentschel J, Duffy L, Baldus K, Cassell GH: 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–S153.
- 90Jalava J, Mantymaa ML, Ekblad U, Toivanen P, Skurnik M, Lassila O, Alanen A: Bacterial 16S rDNA polymerase chain reaction in the detection of intra-amniotic infection. Br J Obstet Gynaecol 1996; 103: 664–669.
- 91Hitti J, Riley DE, Krohn MA, Hillier SL, Agnew KJ, Krieger JN, Eschenbach DA: Broad-spectrum bacterial rDNA polymerase chain reaction assay for detecting amniotic fluid infection among women in premature labor. Clin Infect Dis 1997; 24: 1228–1232.
- 92Bearfield C, Davenport ES, Sivapathasundaram V, Allaker RP: Possible association between amniotic fluid micro-organism infection and microflora in the mouth. BJOG 2002; 109: 527–533.
- 93Gerber 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: 518–521.
- 94Yoon BH, Romero R, Lim JH, Shim SS, Hong JS, Shim JY, Jun JK: 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: 919–924.
- 95Perni SC, Vardhana S, Korneeva I, Tuttle SL, Paraskevas LR, Chasen ST, Kalish RB, Witkin SS: Mycoplasma hominis and Ureaplasma urealyticum in midtrimester amniotic fluid: association with amniotic fluid cytokine levels and pregnancy outcome. Am J Obstet Gynecol 2004; 191: 1382–1386.
- 96Yi J, Yoon BH, Kim EC: Detection and biovar discrimination of Ureaplasma urealyticum by real-time PCR. Mol Cell Probes 2005; 19: 255–260.
- 97Leon R, Silva N, Ovalle A, Chaparro A, Ahumada A, Gajardo M, Martinez M, Gamonal J: Detection of Porphyromonas gingivalis in the amniotic fluid in pregnant women with a diagnosis of threatened premature labor. J Periodontol 2007; 78: 1249–1255.
- 98Oh KJ, Lee KA, Sohn YK, Park CW, Hong JS, Romero R, Yoon BH: Intraamniotic infection with genital mycoplasmas exhibits a more intense inflammatory response than intraamniotic infection with other microorganisms in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 2010; 203: 211 e211-218.
- 99DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, Gotsch F, Kim CJ, Erez O, Edwin S, Relman DA: Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS ONE 2008; 3: e3056.
- 100Han YW, Shen T, Chung P, Buhimschi IA, Buhimschi CS: Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth. J Clin Microbiol 2009; 47: 38–47.
- 101DiGiulio DB, Romero R, Kusanovic JP, Gomez R, Kim CJ, Seok KS, Gotsch F, Mazaki-Tovi S, Vaisbuch E, Sanders K, Bik EM, Chaiworapongsa T, Oyarzun E, Relman DA: 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.
- 102Rodriguez N, Fernandez C, Zamora Y, Berdasquera D, Rivera JA: Detection of Ureaplasma urealyticum and Ureaplasma parvum in amniotic fluid: association with pregnancy outcomes. J Matern Fetal Neonatal Med 2011; 24: 47–50.
- 103Jungkind D: Tech. Sight. Molecular testing for infectious disease. Science 2001; 294: 1553–1555.
- 104Singh DV: Hexaplex PCR for rapid detection of virulence factors. Expert Rev Mol Diagn 2003; 3: 781–784.
- 105Bhattacharya S: Early diagnosis of resistant pathogens: how can it improve antimicrobial treatment? Virulence 2013; 4: 172–184.
- 106Ecker DJ, Sampath R, Blyn LB, Eshoo MW, Ivy C, Ecker JA, Libby B, Samant V, Sannes-Lowery KA, Melton RE, Russell K, Freed N, Barrozo C, Wu J, Rudnick K, Desai A, Moradi E, Knize DJ, Robbins DW, Hannis JC, Harrell PM, Massire C, Hall TA, Jiang Y, Ranken R, Drader JJ, White N, McNeil JA, Crooke ST, Hofstadler SA: Rapid identification and strain-typing of respiratory pathogens for epidemic surveillance. Proc Natl Acad Sci USA 2005; 102: 8012–8017.
- 107Ecker DJ, Sampath R, Willett P, Wyatt JR, Samant V, Massire C, Hall TA, Hari K, McNeil JA, Buchen-Osmond C, Budowle B: The Microbial Rosetta Stone Database: a compilation of global and emerging infectious microorganisms and bioterrorist threat agents. BMC Microbiol 2005; 5: 19.
- 108Hofstadler SA, Sampath R, Blyn LB, Eshoo MW, Hall TA, Jiang Y, Drader JJ, Hannis JC, Sannes-Lowery KA, Cummins LL, Libby B, Walcott DJ, Schink A, Massire C, Ranken R, Gutierrez J, Manalili S, Ivy C, Melton R, Levene H, Barret-Wilt G, Li F, Zapp V, White N, Samant V, McNeil JA, Knize D, Robbins D, Rudnick K, Desai A, Moradi E, Ecker DJ: TIGER: the universal biosensor. Int J Mass Spectrom 2005; 242: 23–41.
- 109Sampath R, Hall TA, Massire C, Li F, Blyn LB, Eshoo MW, Hofstadler SA, Ecker DJ: Rapid identification of emerging infectious agents using PCR and electrospray ionization mass spectrometry. Ann N Y Acad Sci 2007; 1102: 109–120.
- 110Ecker DJ, Sampath R, Massire C, Blyn LB, Hall TA, Eshoo MW, Hofstadler SA: Ibis T5000: a universal biosensor approach for microbiology. Nat Rev Microbiol 2008; 6: 553–558.
- 111Ecker DJ, Massire C, Blyn LB, Hofstadler SA, Hannis JC, Eshoo MW, Hall TA, Sampath R: Molecular Genotyping of Microbes by Multilocus PCR and Mass Spectrometry: A new tool for Hospital Infection Control and Public Health Surveillance. In Molecular Epidemiology of Microorganisms, Methods in Molecular Biology, DA Caugant (ed). New York, Humana Press, a part of Springer Science + Business Media, 2009, pp 71–87.
- 112Ecker DJ, Sampath R, Li H, Massire C, Matthews HE, Toleno D, Hall TA, Blyn LB, Eshoo MW, Ranken R, Hofstadler SA, Tang YW: New technology for rapid molecular diagnosis of bloodstream infections. Expert Rev Mol Diagn 2010; 10: 399–415.
- 113Wolk 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.
- 114Metzgar D, Frinder M, Lovari R, Toleno D, Massire C, Blyn LB, Ranken R, Carolan HE, Hall TA, Moore D, Hansen CJ, Sampath R, Ecker DJ: Broad-spectrum biosensor capable of detecting and identifying diverse bacterial and Candida species in blood. J Clin Microbiol 2013; 51: 2670–2678.
- 115Sampath R, Hofstadler SA, Blyn LB, Eshoo MW, Hall TA, Massire C, Levene HM, Hannis JC, Harrell PM, Neuman B, Buchmeier MJ, Jiang Y, Ranken R, Drader JJ, Samant V, Griffey RH, McNeil JA, Crooke ST, Ecker DJ: Rapid identification of emerging pathogens: coronavirus. Emerg Infect Dis 2005; 11: 373–379.
- 116Ecker JA, Massire C, Hall TA, Ranken R, Pennella TT, Agasino Ivy C, Blyn LB, Hofstadler SA, Endy TP, Scott PT, Lindler L, Hamilton T, Gaddy C, Snow K, Pe M, Fishbain J, Craft D, Deye G, Riddell S, Milstrey E, Petruccelli B, Brisse S, Harpin V, Schink A, Ecker DJ, Sampath R, Eshoo MW: Identification of Acinetobacter species and genotyping of Acinetobacter baumannii by multilocus PCR and mass spectrometry. J Clin Microbiol 2006; 44: 2921–2932.
- 117Sampath R, Russell KL, Massire C, Eshoo MW, Harpin V, Blyn LB, Melton R, Ivy C, Pennella T, Li F, Levene H, Hall TA, Libby B, Fan N, Walcott DJ, Ranken R, Pear M, Schink A, Gutierrez J, Drader J, Moore D, Metzgar D, Addington L, Rothman R, Gaydos CA, Yang S, St George K, Fuschino ME, Dean AB, Stallknecht DE, Goekjian G, Yingst S, Monteville M, Saad MD, Whitehouse CA, Baldwin C, Rudnick KH, Hofstadler SA, Lemon SM, Ecker DJ: Global surveillance of emerging Influenza virus genotypes by mass spectrometry. PLoS ONE 2007; 2: e489.
- 118Eshoo MW, Whitehouse CA, Zoll ST, Massire C, Pennella TT, Blyn LB, Sampath R, Hall TA, Ecker JA, Desai A, Wasieloski LP, Li F, Turell MJ, Schink A, Rudnick K, Otero G, Weaver SC, Ludwig GV, Hofstadler SA, Ecker DJ: Direct broad-range detection of alphaviruses in mosquito extracts. Virology 2007; 368: 286–295.
- 119Blyn LB, Hall TA, Libby B, Ranken R, Sampath R, Rudnick K, Moradi E, Desai A, Metzgar D, Russell KL, Freed NE, Balansay M, Broderick MP, Osuna MA, Hofstadler SA, Ecker DJ: Rapid detection and molecular serotyping of adenovirus by use of PCR followed by electrospray ionization mass spectrometry. J Clin Microbiol 2008; 46: 644–651.
- 120Hannis JC, Manalili SM, Hall TA, Ranken R, White N, Sampath R, Blyn LB, Ecker DJ, Mandrell RE, Fagerquist CK, Bates AH, Miller WG, Hofstadler SA: High-resolution genotyping of Campylobacter species by use of PCR and high-throughput mass spectrometry. J Clin Microbiol 2008; 46: 1220–1225.
- 121Wolk DM, Blyn LB, Hall TA, Sampath R, Ranken R, Ivy C, Melton R, Matthews H, White N, Li F, Harpin V, Ecker DJ, Limbago B, McDougal LK, Wysocki VH, Cai M, Carroll KC: Pathogen profiling: rapid molecular characterization of Staphylococcus aureus by PCR/electrospray ionization-mass spectrometry and correlation with phenotype. J Clin Microbiol 2009; 47: 3129–3137.
- 122Hujer KM, Hujer AM, Endimiani A, Thomson JM, Adams MD, Goglin K, Rather PN, Pennella TT, Massire C, Eshoo MW, Sampath R, Blyn LB, Ecker DJ, Bonomo RA: Rapid determination of quinolone resistance in Acinetobacter spp. J Clin Microbiol 2009; 47: 1436–1442.
- 123Metzgar D, Baynes D, Myers CA, Kammerer P, Unabia M, Faix DJ, Blair PJ: Initial identification and characterization of an emerging zoonotic influenza virus prior to pandemic spread. J Clin Microbiol 2010; 48: 4228–4234.
- 124Deyde VM, Sampath R, Garten RJ, Blair PJ, Myers CA, Massire C, Matthews H, Svoboda P, Reed MS, Pohl J, Klimov AI, Gubareva LV: Genomic signature-based identification of influenza A viruses using RT-PCR/electro-spray ionization mass spectrometry (ESI-MS) technology. PLoS ONE 2010; 5: e13293.
- 125Eshoo MW, Crowder CD, Li H, Matthews HE, Meng S, Sefers SE, Sampath R, Stratton CW, Blyn LB, Ecker DJ, Tang YW: Detection and identification of Ehrlichia species in blood by use of PCR and electrospray ionization mass spectrometry. J Clin Microbiol 2010; 48: 472–478.
- 126Chen KF, Blyn L, Rothman RE, Ramachandran P, Valsamakis A, Ecker D, Sampath R, Gaydos CA: Reverse transcription polymerase chain reaction and electrospray ionization mass spectrometry for identifying acute viral upper respiratory tract infections. Diagn Microbiol Infect Dis 2011; 69: 179–186.
- 127Kaleta EJ, Clark AE, Cherkaoui A, Wysocki VH, Ingram EL, Schrenzel J, Wolk DM: 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: 1057–1067.
- 128Massire C, Ivy CA, Lovari R, Kurepina N, Li H, Blyn LB, Hofstadler SA, Khechinashvili G, Stratton CW, Sampath R, Tang YW, Ecker DJ, Kreiswirth BN: 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: 908–917.
- 129Gu Z, Hall TA, Frinder M, Walsh TJ, Hayden RT: Evaluation of repetitive sequence PCR and PCR-mass spectrometry for the identification of clinically relevant Candida species. Med Mycol 2012; 50: 259–265.
- 130Bhatia NS, Farrell JJ, Sampath R, Ranken R, Rounds MA, Ecker DJ, Bonomo RA: Identification of Streptococcus intermedius central nervous system infection by use of PCR and electrospray ionization mass spectrometry. J Clin Microbiol 2012; 50: 4160–4162.
- 131Schuetz AN, Huard RC, Eshoo MW, Massire C, Della-Latta P, Wu F, Jenkins SG: 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: 14–19.
- 132Brinkman CL, Vergidis P, Uhl JR, Pritt BS, Cockerill FR, Steckelberg JM, Baddour LM, Maleszewski JJ, Edwards WD, Sampath R, Patel R: 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: 2040–2046.
- 133Farrell JJ, Sampath R, Ecker DJ, Bonomo RA: ‘Salvage Microbiology’: Detection of Bacteria Directly from Clinical Specimens following Initiation of Antimicrobial Treatment. PLoS ONE 2013; 8: e66349.
- 134Jordana-Lluch E, Carolan HE, Gimenez M, Sampath R, Ecker DJ, Quesada MD, Modol JM, Armestar F, Blyn LB, Cummins LL, Ausina V, Martro E: Rapid diagnosis of bloodstream infections with PCR followed by mass spectrometry. PLoS ONE 2013; 8: e62108.
- 135Eshoo MW, Crowder CC, Rebman AW, Rounds MA, Matthews HE, Picuri JM, Soloski MJ, Ecker DJ, Schutzer SE, Aucott JN: Direct molecular detection and genotyping of Borrelia burgdorferi from whole blood of patients with early Lyme disease. PLoS ONE 2012; 7: e36825.
- 136Kaleta EJ, Clark AE, Johnson DR, Gamage DC, Wysocki VH, Cherkaoui A, Schrenzel J, Wolk DM: Use of PCR coupled with electrospray ionization mass spectrometry for rapid identification of bacterial and yeast bloodstream pathogens from blood culture bottles. J Clin Microbiol 2011; 1: 345–353.
- 137 A broad range of tests to meet your needs. www.athogen.com/consulting-services/microbial-tests.html. In.
- 138Legoff J, Feghoul L, Mercier-Delarue S, Dalle JH, Scieux C, Cherot J, Sicre de Fontbrune F, Baruchel A, Socie G, Simon F: 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; 12: 4186–4192.
- 139Pacora P, Chaiworapongsa T, Maymon E, Kim YM, Gomez R, Yoon BH, Ghezzi F, Berry SM, Qureshi F, Jacques SM, Kim JC, Kadar N, Romero R: Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med 2002; 11: 18–25.
- 140Redline RW, Heller D, Keating S, Kingdom J: Placental diagnostic criteria and clinical correlation–a workshop report. Placenta 2005; 26(Suppl. A): S114–S117.
- 141Redline RW: Inflammatory responses in the placenta and umbilical cord. Semin Fetal Neonatal Med 2006; 11: 296–301.
- 142Kim KW, Romero R, Park HS, Park CW, Shim SS, Jun JK, Yoon BH: 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 e291-295.
- 143DiGiulio DB, Gervasi M, Romero R, Mazaki-Tovi S, Vaisbuch E, Kusanovic JP, Seok KS, Gomez R, Mittal P, Gotsch F, Chaiworapongsa T, Oyarzun E, Kim CJ, Relman DA: Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods. J Perinat Med 2010; 38: 503–513.
- 144DiGiulio DB, Gervasi MT, Romero R, Vaisbuch E, Mazaki-Tovi S, Kusanovic JP, Seok KS, Gomez R, Mittal P, Gotsch F, Chaiworapongsa T, Oyarzun E, Kim CJ, Relman DA: Microbial invasion of the amniotic cavity in pregnancies with small-for-gestational-age fetuses. J Perinat Med 2010; 38: 495–502.
- 145Romero R, Korzeniewski SJ: Are infants born by elective cesarean delivery without labor at risk for developing immune disorders later in life? Am J Obstet Gynecol 2013; 208: 243–246.
- 146Gray DJ, Robinson HB, Malone J, Thomson RB Jr: Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum. Prenat Diagn 1992; 12: 111–117.
- 147Seong HS, Lee SE, Kang JH, Romero R, Yoon BH: 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 e371-375.
- 148Gervasi MT, Romero R, Bracalente G, Erez O, Dong Z, Hassan SS, Yeo L, Yoon BH, Chaiworapongsa T: 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: 329–343.
- 149Yoon BH, Romero R, Moon J, Chaiworapongsa T, Espinoza J, Kim YM, Edwin S, Kim JC, Camacho N, Bujold E, Gomez R: Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation. J Matern Fetal Neonatal Med 2003; 13: 32–38.
- 150Lee SE, Romero R, Kim CJ, Shim SS, Yoon BH: Funisitis in term pregnancy is associated with microbial invasion of the amniotic cavity and intra-amniotic inflammation. J Matern Fetal Neonatal Med 2006; 19: 693–697.
- 151McLean LK, Chehab FF, Goldberg JD: Detection of viral deoxyribonucleic acid in the amniotic fluid of low-risk pregnancies by polymerase chain reaction. Am J Obstet Gynecol 1995; 173: 1282–1286.
- 152Van den Veyver IB, Ni J, Bowles N, Carpenter RJ Jr, Weiner CP, Yankowitz J, Moise KJ Jr, Henderson J, Towbin JA: Detection of intrauterine viral infection using the polymerase chain reaction. Mol Genet Metab 1998; 63: 85–95.
- 153Baschat AA, Towbin J, Bowles NE, Harman CR, Weiner CP: Prevalence of viral DNA in amniotic fluid of low-risk pregnancies in the second trimester. J Matern Fetal Neonatal Med 2003; 13: 381–384.
- 154Gervasi MT, Romero R, Bracalente G, Chaiworapongsa T, Erez O, Dong Z, Hassan SS, Yeo L, Yoon BH, Mor G, Barzon L, Franchin E, Militello V, Palu G: Viral invasion of the amniotic cavity (VIAC) in the midtrimester of pregnancy. J Matern Fetal Neonatal Med 2012; 25: 2002–2013.
- 155Berg TG, Philpot KL, Welsh MS, Sanger WG, Smith CV: Ureaplasma/Mycoplasma-infected amniotic fluid: pregnancy outcome in treated and nontreated patients. J Perinatol 1999; 19: 275–277.
- 156Goncalves LF, Chaiworapongsa T, Romero R: Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev 2002; 8: 3–13.
- 157Hitti J, Tarczy-Hornoch P, Murphy J, Hillier SL, Aura J, Eschenbach DA: Amniotic fluid infection, cytokines, and adverse outcome among infants at 34 weeks’ gestation or less. Obstet Gynecol 2001; 98: 1080–1088.
- 158Soto E, Romero R, Richani K, Yoon BH, Chaiworapongsa T, Vaisbuch E, Mittal P, Erez O, Gotsch F, Mazor M, Kusanovic JP: Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection. J Matern Fetal Neonatal Med 2009; 22: 983–992.
- 159Kacerovsky M, Pliskova L, Bolehovska R, Skogstrand K, Hougaard DM, Tsiartas P, Jacobsson B: The impact of the microbial load of genital mycoplasmas and gestational age on the intensity of intraamniotic inflammation. Am J Obstet Gynecol 2012; 206: 342 e341-348.
- 160Romero R, Gonzalez R, Sepulveda W, Brandt F, Ramirez M, Sorokin Y, Mazor M, Treadwell MC, Cotton DB: 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: 1086–1091.
- 161Mays JK, Figueroa R, Shah J, Khakoo H, Kaminsky S, Tejani N: Amniocentesis for selection before rescue cerclage. Obstet Gynecol 2000; 95: 652–655.
- 162Lee SE, Romero R, Park CW, Jun JK, Yoon BH: The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency. Am J Obstet Gynecol 2008; 198: 633 e631-638.
- 163Bujold E, Morency AM, Rallu F, Ferland S, Tetu A, Duperron L, Audibert F, Laferriere C: Bacteriology of amniotic fluid in women with suspected cervical insufficiency. J Obstet Gynaecol Can 2008; 30: 882–887.
- 164Romero R, Mazor M, Munoz H, Gomez R, Galasso M, Sherer DM: The preterm labor syndrome. Ann N Y Acad Sci 1994; 734: 414–429.
- 165Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, Chaiworapongsa T, Mazor M: The preterm parturition syndrome. BJOG 2006; 113(Suppl. 3): 17–42.
- 166Relman DA: The biological century: coming to terms with risk in the life sciences. Nat Immunol 2010; 11: 275–278.
- 167Relman DA: Microbial genomics and infectious diseases. N Engl J Med 2011; 365: 347–357.
- 168 Centers for Disease Control (CDC): Increase in National Hospital Discharge Survey rates for septicemia–United States, 1979–1987. MMWR Morb Mortal Wkly Rep 1990; 39: 31–34.
- 169Houpikian P, Raoult D: Traditional and molecular techniques for the study of emerging bacterial diseases: one laboratory's perspective. Emerg Infect Dis 2002; 8: 122–131.
- 170Fournier PE, Raoult D: Nonculture Laboratory Methods for the Diagnosis of Infectious Endocarditis. Curr Infect Dis Rep 1999; 1: 136–141.
- 171Yeo SF, Wong B: Current status of nonculture methods for diagnosis of invasive fungal infections. Clin Microbiol Rev 2002; 15: 465–484.
- 172White PL, Archer AE, Barnes RA: Comparison of non-culture-based methods for detection of systemic fungal infections, with an emphasis on invasive Candida infections. J Clin Microbiol 2005; 43: 2181–2187.
- 173Jones TF, Gerner-Smidt P: Nonculture diagnostic tests for enteric diseases. Emerg Infect Dis 2012; 18: 513–514.
- 174Didelot X, Bowden R, Wilson DJ, Peto TE, Crook DW: Transforming clinical microbiology with bacterial genome sequencing. Nat Rev Genet 2012; 13: 601–612.
- 175Fitzgerald T: In vitro cultivation of Treponema pallidum: a review. Bull World Health Organ 1981; 59: 787–101.
- 176Ho EL, Lukehart SA: Syphilis: using modern approaches to understand an old disease. J Clin Invest 2011; 121: 4584–4592.
- 177Pace NR: A molecular view of microbial diversity and the biosphere. Science 1997; 276: 734–740.
- 178Relman DA: The search for unrecognized pathogens. Science 1999; 284: 1308–1310.
- 179Amann R: Who is out there? Microbial aspects of biodiversity. Syst Appl Microbiol 2000; 23: 1–8.
- 180Petrosino JF, Highlander S, Luna RA, Gibbs RA, Versalovic J: Metagenomic pyrosequencing and microbial identification. Clin Chem 2009; 55: 856–866.
- 181Flores GE, Henley JB, Fierer N: A direct PCR approach to accelerate analyses of human-associated microbial communities. PLoS ONE 2012; 7: e44563.
- 182Wilson KH, Blitchington R, Frothingham R, Wilson JA: Phylogeny of the Whipple's-disease-associated bacterium. Lancet 1991; 338: 474–475.
- 183Relman DA, Schmidt TM, MacDermott RP, Falkow S: Identification of the uncultured bacillus of Whipple's disease. N Engl J Med 1992; 327: 293–301.
- 184Bottger EC, Teske A, Kirschner P, Bost S, Chang HR, Beer V, Hirschel B: Disseminated ‘Mycobacterium genavense’ infection in patients with AIDS. Lancet 1992; 340: 76–80.
- 185Anderson BE, Dawson JE, Jones DC, Wilson KH: Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. J Clin Microbiol 1991; 29: 2838–2842.
- 186Welch DF, Pickett DA, Slater LN, Steigerwalt AG, Brenner DJ: Rochalimaea henselae sp. nov., a cause of septicemia, bacillary angiomatosis, and parenchymal bacillary peliosis. J Clin Microbiol 1992; 30: 275–280.
- 187Brenner DJ, O'Connor SP, Winkler HH, Steigerwalt AG: Proposals to unify the genera Bartonella and Rochalimaea, with descriptions of Bartonella quintana comb. nov., Bartonella vinsonii comb. nov., Bartonella henselae comb. nov., and Bartonella elizabethae comb. nov., and to remove the family Bartonellaceae from the order Rickettsiales. Int J Syst Bacteriol 1993; 43: 777–786.
- 188Bergmans AM, Groothedde JW, Schellekens JF, van Embden JD, Ossewaarde JM, Schouls LM: Etiology of cat scratch disease: comparison of polymerase chain reaction detection of Bartonella (formerly Rochalimaea) and Afipia felis DNA with serology and skin tests. J Infect Dis 1995; 171: 916–923.
- 189Chen K, Neimark H, Rumore P, Steinman CR: Broad range DNA probes for detecting and amplifying eubacterial nucleic acids. FEMS Microbiol Lett 1989; 48: 19–24.
- 190Greisen K, Loeffelholz M, Purohit A, Leong D: PCR primers and probes for the 16S rRNA gene of most species of pathogenic bacteria, including bacteria found in cerebrospinal fluid. J Clin Microbiol 1994; 32: 335–351.
- 191Holst RM, Mattsby-Baltzer I, Wennerholm UB, Hagberg H, Jacobsson B: 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: 551–557.
- 192Holst RM, Jacobsson B, Hagberg H, Wennerholm UB: 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: 768–774.
- 193Oh KJ, Lee SE, Jung H, Kim G, Romero R, Yoon BH: Detection of ureaplasmas by the polymerase chain reaction in the amniotic fluid of patients with cervical insufficiency. J Perinat Med 2010; 38: 261–268.
- 194Kacerovsky M, Pliskova L, Bolehovska R, Musilova I, Hornychova H, Tambor V, Jacobsson B: The microbial load with genital mycoplasmas correlates with the degree of histologic chorioamnionitis in preterm PROM. Am J Obstet Gynecol 2011; 205:213: e211–217.
- 195Holst RM, Hagberg H, Wennerholm UB, Skogstrand K, Thorsen P, Jacobsson B: 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: 240–249.
- 196Markenson GR, Martin RK, Tillotson-Criss M, Foley KS, Stewart RS Jr, Yancey M: 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: 1471–1477.
- 197Gardella C, Riley DE, Hitti J, Agnew K, Krieger JN, Eschenbach D: Identification and sequencing of bacterial rDNAs in culture-negative amniotic fluid from women in premature labor. Am J Perinatol 2004; 21: 319–323.
- 198Miralles R, Hodge R, McParland PC, Field DJ, Bell SC, Taylor DJ, Grant WD, Kotecha S: Relationship between antenatal inflammation and antenatal infection identified by detection of microbial genes by polymerase chain reaction. Pediatr Res 2005; 57: 570–577.
- 199Marconi C, de Andrade Ramos BR, Peracoli JC, Donders GG, da Silva MG: 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: 549–556.
- 200Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, Kornegay J, Jackson B, Moye J, Hanson C, Zorrilla C, Lew JF: Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med 1999; 341: 394–402.
- 201Read JS: Cesarean section delivery to prevent vertical transmission of human immunodeficiency virus type 1. Associated risks and other considerations. Ann N Y Acad Sci 2000; 918: 115–121.
- 202Marcollet A, Goffinet F, Firtion G, Pannier E, Le Bret T, Brival ML, Mandelbrot L: Differences in postpartum morbidity in women who are infected with the human immunodeficiency virus after elective cesarean delivery, emergency cesarean delivery, or vaginal delivery. Am J Obstet Gynecol 2002; 186: 784–789.
- 203Gross E, Burr CK: HIV counseling and testing in pregnancy. N J Med 2003; 100: 21–6; quiz 67-8.
- 204Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB, Clark JE: Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep 2006; 55: 1–17; quiz CE1-14.
- 205Senise J, Bonafe S, Castelo A: The management of HIV-infected pregnant women. Curr Opin Obstet Gynecol 2012; 24: 395–401.
- 206Cotter AM, Brookfield KF, Duthely LM, Gonzalez Quintero VH, Potter JE, O'Sullivan MJ: Duration of membrane rupture and risk of perinatal transmission of HIV-1 in the era of combination antiretroviral therapy. Am J Obstet Gynecol 2012; 207: 482 e481-485.
- 207Mary C, Faraut F, Lascombe L, Dumon H: Quantification of Leishmania infantum DNA by a real-time PCR assay with high sensitivity. J Clin Microbiol 2004; 42: 5249–5255.
- 208Pourabbas B, Ghadimi Moghadam A, Pouladfar G, Rezaee Z, Alborzi A: Quantification of Leishmania infantum kinetoplast DNA for monitoring the response to meglumine antimoniate therapy in visceral leishmaniasis. Am J Trop Med Hyg 2013; 88: 868–871.
- 209Molina I, Fisa R, Riera C, Falco V, Elizalde A, Salvador F, Crespo M, Curran A, Lopez-Chejade P, Tebar S, Perez-Hoyos S, Ribera E, Pahissa A: Ultrasensitive real-time PCR for the clinical management of visceral leishmaniasis in HIV-Infected patients. Am J Trop Med Hyg 2013; 89: 105–110.
- 210Lay ML, Lucas RM, Ratnamohan M, Taylor J, Ponsonby AL, Dwyer DE: Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye. Virol J 2010; 7: 252.
- 211Sakamoto Y, Mariya Y, Kubo K: Quantification of Epstein-Barr virus DNA is helpful for evaluation of chronic active Epstein-Barr virus infection. Tohoku J Exp Med 2012; 227: 307–311.
- 212Ruf S, Wagner HJ: Determining EBV load: current best practice and future requirements. Expert Rev Clin Immunol 2013; 9: 139–151.
- 213Rello J, Lisboa T, Lujan M, Gallego M, Kee C, Kay I, Lopez D, Waterer GW: Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest 2009; 136: 832–840.
- 214Werno AM, Anderson TP, Murdoch DR: Association between pneumococcal load and disease severity in adults with pneumonia. J Med Microbiol 2012; 61: 1129–1135.
- 215Romero R, Hanaoka S, Mazor M, Athanassiadis AP, Callahan R, Hsu YC, Avila C, Nores J, Jimenez C: Meconium-stained amniotic fluid: a risk factor for microbial invasion of the amniotic cavity. Am J Obstet Gynecol 1991; 164: 859–862.
- 216Romero R, Sepulveda W, Kenney JS, Archer LE, Allison AC, Sehgal PB: Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity. Ciba Found Symp 1992: 205–20; discussion 220-3.
- 217Romero R, Gomez R, Galasso M, Munoz H, Acosta L, Yoon BH, Svinarich D, Cotton DB: Macrophage inflammatory protein-1 alpha in term and preterm parturition: effect of microbial invasion of the amniotic cavity. Am J Reprod Immunol 1994; 32: 108–113.
- 218Romero R, Gomez R, Mazor M, Ghezzi F, Yoon BH: The preterm labor syndrome. In Preterm Labor, MG Elder, R Romero, RF Lamont (eds). New York, Churchill Livingstone, 1997, pp 29–49.
- 219Yoon BH, Romero R, Park JS, Chang JW, Kim YA, Kim JC, Kim KS: 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: 1254–1260.
- 220Romero R, Manogue KR, Mitchell MD, Wu YK, Oyarzun E, Hobbins JC, Cerami A: 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: 336–341.
- 221Romero R, Avila S, Sepulveda W: The role of systemic and intrauterine infection in preterm labor. In Preterm Birth: Causes, Prevention, and Management, A Fuchs, F Fuchs, P Stubblefield (eds). New York, McGraw-Hill Inc., 1993, pp 97.
- 222Baumann P, Romero R, Berry S, Gomez R, McFarlin B, Araneda H, Cotton DB, Fidel P: 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: 184–193.
- 223Hillier SL, Witkin SS, Krohn MA, Watts DH, Kiviat NB, Eschenbach DA: The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol 1993; 81: 941–948.
- 224Gomez R, Ghezzi F, Romero R, Munoz H, Tolosa JE, Rojas I: Premature labor and intra-amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology. Clin Perinatol 1995; 22: 281–342.
- 225Gomez R, Ghezzi F, Romero R, Yoon BH, Mazor M, Berry SM: Two thirds of human fetuses with microbial invasion of the amniotic cavity have a detectable systemic cyto-kine response before birth. Am J Obstet Gynecol 1997; 176: S14.
10.1016/S0002-9378(97)80102-0 Google Scholar
- 226Romero R, Gomez R, Ghezzi F, Yoon BH, Mazor M, Edwin SS, Berry SM: A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol 1998; 179: 186–193.
- 227Hsu CD, Meaddough E, Hong SF, Aversa K, Lu LC, Copel JA: Elevated amniotic fluid nitric oxide metabolites and interleukin-6 in intra-amniotic infection. J Soc Gynecol Investig 1998; 5: 21–24.
- 228Hsu CD, Meaddough E, Aversa K, Hong SF, Lu LC, Jones DC, Copel JA: Elevated amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 in intra-amniotic infection. Am J Obstet Gynecol 1998; 179: 1267–1270.
- 229Pacora P, Romero R, Maymon E, Gervasi MT, Gomez R, Edwin SS, Yoon BH: Participation of the novel cytokine interleukin 18 in the host response to intra-amniotic infection. Am J Obstet Gynecol 2000; 183: 1138–1143.
- 230Athayde N, Romero R, Maymon E, Gomez R, Pacora P, Yoon BH, Edwin SS: Interleukin 16 in pregnancy, parturition, rupture of fetal membranes, and microbial invasion of the amniotic cavity. Am J Obstet Gynecol 2000; 182: 135–141.
- 231Keelan JA, Yang J, Romero RJ, Chaiworapongsa T, Marvin KW, Sato TA, Mitchell MD: 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: 253–259.
- 232Esplin MS, Romero R, Chaiworapongsa T, Kim YM, Edwin S, Gomez R, Mazor M, Adashi EY: 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: 365–373.
- 233Chaiworapongsa T, Romero R, Espinoza J, Kim YM, Edwin S, Bujold E, Gomez R, Kuivaniemi H: Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity. J Matern Fetal Neonatal Med 2005; 18: 405–416.
- 234Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel L, Hassan S: The role of inflammation and infection in preterm birth. Semin Reprod Med 2007; 25: 21–39.
- 235Kacerovsky M, Musilova I, Khatibi A, Skogstrand K, Hougaard DM, Tambor V, Tosner J, Jacobsson B: Intraamniotic inflammatory response to bacteria: analysis of multiple amniotic fluid proteins in women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med 2012; 25: 2014–2019.
- 236Shim SH, Yoon BH, Romero R, Hong JS, Kim G, Sohn YK, Park JS, Jun JK, Syn HC: The frequency and the clinical significant of intraamniotic inflammation in patients with preterm premature rupture of membrane. Am J Obstet Gynecol 2003; 189: S83.
- 237Shim SS, Romero R, Hong JS, Park CW, Jun JK, Kim BI, Yoon BH: Clinical significance of intra-amniotic inflammation in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 2004; 191: 1339–1345.
- 238Lee SE, Romero R, Jung H, Park CW, Park JS, Yoon BH: 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 e291-296.
- 239Wenstrom KD, Andrews WW, Bowles NE, Towbin JA, Hauth JC, Goldenberg RL: Intrauterine viral infection at the time of second trimester genetic amniocentesis. Obstet Gynecol 1998; 92: 420–424.
- 240Naresh A, Simhan H: Absence of viruses in amniotic fluid of women with PPROM: a case series. J Reprod Immunol 2012; 96: 79–83.
- 241Bopegamage S, Kacerovsky M, Tambor V, Musilova I, Sarmirova S, Snelders E, de Jong AS, Vari SG, Melchers WJ, Galama JM: Preterm prelabor rupture of membranes (PPROM) is not associated with presence of viral genomes in the amniotic fluid. J Clin Virol 2013; 3: 559–563.
- 242Cardenas I, Means RE, Aldo P, Koga K, Lang SM, Booth CJ, Manzur A, Oyarzun E, Romero R, Mor G: Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J Immunol 2010; 185: 1248–1257.
- 243Cardenas I, Mor G, Aldo P, Lang SM, Stabach P, Sharp A, Romero R, Mazaki-Tovi S, Gervasi M, Means RE: Placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis. Am J Reprod Immunol 2011; 65: 110–117.
- 244Hament JM, Kimpen JL, Fleer A, Wolfs TF: Respiratory viral infection predisposing for bacterial disease: a concise review. FEMS Immunol Med Microbiol 1999; 26: 189–195.
- 245McCullers JA: Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev 2006; 19: 571–582.
- 246Morens DM, Taubenberger JK, Fauci AS: Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008; 198: 962–970.
- 247Brundage JF, Shanks GD: Deaths from bacterial pneumonia during 1918-19 influenza pandemic. Emerg Infect Dis 2008; 14: 1193–1199.
- 248Racicot K, Cardenas I, Wunsche V, Aldo P, Guller S, Means RE, Romero R, Mor G: Viral infection of the pregnant cervix predisposes to ascending bacterial infection. J Immunol 2013; 191: 934–941.
- 249Smith CJ, Osborn AM: Advantages and limitations of quantitative PCR (Q-PCR)-based approaches in microbial ecology. FEMS Microbiol Ecol 2009; 67: 6–20.
- 250Katsoulis J, Heitz-Mayfield LJ, Weibel M, Hirschi R, Lang NP, Persson GR: Impact of sample storage on detection of periodontal bacteria. Oral Microbiol Immunol 2005; 20: 128–130.
- 251von Wintzingerode F, Gobel UB, Stackebrandt E: Determination of microbial diversity in environmental samples: pitfalls of PCR-based rRNA analysis. FEMS Microbiol Rev 1997; 21: 213–229.
- 252Sun W, Dong L, Kaneyama K, Takegami T, Segami N: Bacterial diversity in synovial fluids of patients with TMD determined by cloning and sequencing analysis of the 16S ribosomal RNA gene. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105: 566–571.
- 253Hong PY, Croix JA, Greenberg E, Gaskins HR, Mackie RI: Pyrosequencing-based analysis of the mucosal microbiota in healthy individuals reveals ubiquitous bacterial groups and micro-heterogeneity. PLoS ONE 2011; 6: e25042.
- 254Vaneechoutte M, Janssens M, Avesani V, Delmee M, Deschaght P: Description of Acidovorax wautersii sp. nov. to accommodate clinical isolates and an environmental isolate, most closely related to Acidovorax avenae. Int J Syst Evol Microbiol 2013; 63: 2203–2206.
- 255Cox SM, Sherman ML, Leveno KJ: Randomized investigation of magnesium sulfate for prevention of preterm birth. Am J Obstet Gynecol 1990; 163: 767–772.
- 256 The Canadian Preterm Labor Investigators Group: Treatment of preterm labor with the beta-adrenergic agonist ritodrine. N Engl J Med 1992; 327: 308–312.
- 257Papatsonis DN, Van Geijn HP, Ader HJ, Lange FM, Bleker OP, Dekker GA: Nifedipine and ritodrine in the management of preterm labor: a randomized multicenter trial. Obstet Gynecol 1997; 90: 230–234.
- 258Romero R, Sibai BM, Sanchez-Ramos L, Valenzuela GJ, Veille JC, Tabor B, Perry KG, Varner M, Goodwin TM, Lane R, Smith J, Shangold G, Creasy GW: An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue. Am J Obstet Gynecol 2000; 182: 1173–1183.
- 259Valenzuela GJ, Sanchez-Ramos L, Romero R, Silver HM, Koltun WD, Millar L, Hobbins J, Rayburn W, Shangold G, Wang J, Smith J, Creasy GW: Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group. Am J Obstet Gynecol 2000; 182: 1184–1190.
- 260Smith GN, Walker MC, Ohlsson A, O'Brien K, Windrim R: Randomized double-blind placebo-controlled trial of transdermal nitroglycerin for preterm labor. Am J Obstet Gynecol 2007; 196: 37 e31-38.
- 261Iams JD, Romero R, Culhane JF, Goldenberg RL: Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet 2008; 371: 164–175.
- 262Conde-Agudelo A, Romero R, Kusanovic JP: Nifedipine in the management of preterm labor: a systematic review and metaanalysis. Am J Obstet Gynecol 2011; 204 res: 134.E1-20.
- 263Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ, Welton NJ: Tocolytic therapy for preterm delivery: systematic review and network meta-analysis. BMJ 2012; 345: e6226.
- 264Conde-Agudelo A, Romero R: Transdermal nitroglycerin for the treatment of preterm labor: a systematic review and metaanalysis. Am J Obstet Gynecol 2013; 6: 551.e1–551.e18.
- 265Hadar E, Melamed N, Aviram A, Raban O, Saltzer L, Hiersch L, Yogev Y: Effect of an oxytocin receptor antagonist (atosiban) on uterine electrical activity. Am J Obstet Gynecol 2013; 209: 384 e381-387.
- 266Sanchez-Ramos L, Kaunitz AM, Gaudier FL, Delke I: Efficacy of maintenance therapy after acute tocolysis: a meta-analysis. Am J Obstet Gynecol 1999; 181: 484–490.
- 267Berkman ND, Thorp JM Jr, Lohr KN, Carey TS, Hartmann KE, Gavin NI, Hasselblad V, Idicula AE: Tocolytic treatment for the management of preterm labor: a review of the evidence. Am J Obstet Gynecol 2003; 188: 1648–1659.
- 268Dodd JM, Crowther CA, Middleton P: Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane Database Syst Rev 2012; 12: CD003927.
- 269Romero R: The child is the father of the man. Prenat Neonat Med 1996; 1: 8–11.
- 270Romero R: Prenatal medicine: the child is the father of the man. 1996. J Matern Fetal Neonatal Med 2009; 22: 636–639.
- 271Romero R, Yeo L, Miranda J, Hassan SS, Conde-Agudelo A, Chaiworapongsa T: A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix. J Perinat Med 2013; 41: 27–44.
- 272Grether JK, Nelson KB: Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997; 278: 207–211.
- 273Dammann 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.
- 274Paneth N: Classifying brain damage in preterm infants. J Pediatr 1999; 134: 527–529.
- 275Gravett 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: 1404–1413.
- 276Grether JK, Nelson KB, Walsh E, Willoughby RE, Redline RW: Intrauterine exposure to infection and risk of cerebral palsy in very preterm infants. Arch Pediatr Adolesc Med 2003; 157: 26–32.
- 277Elovitz MA, Mrinalini C, Sammel MD: Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth. Pediatr Res 2006; 59: 50–55.
- 278Dammann O, Leviton A: Inflammation, brain damage and visual dysfunction in preterm infants. Semin Fetal Neonatal Med 2006; 11: 363–368.
- 279McElrath TF, Allred EN, Boggess KA, Kuban K, O'Shea TM, Paneth N, Leviton A: Maternal antenatal complications and the risk of neonatal cerebral white matter damage and later cerebral palsy in children born at an extremely low gestational age. Am J Epidemiol 2009; 170: 819–828.
- 280O'Shea TM, Allred EN, Dammann O, Hirtz D, Kuban KC, Paneth N, Leviton A: The ELGAN study of the brain and related disorders in extremely low gestational age newborns. Early Hum Dev 2009; 85: 719–725.
- 281Leviton A, Allred EN, Kuban KC, Hecht JL, Onderdonk AB, O'Shea TM, Paneth N: Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. the ELGAN study. Pediatr Res 2010; 67: 95–101.
- 282Burd I, Bentz AI, Chai J, Gonzalez J, Monnerie H, Le Roux PD, Cohen AS, Yudkoff M, Elovitz MA: Inflammation-induced preterm birth alters neuronal morphology in the mouse fetal brain. J Neurosci Res 2010; 88: 1872–1881.
- 283Elovitz MA, Brown AG, Breen K, Anton L, Maubert M, Burd I: Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int J Dev Neurosci 2011; 29: 663–671.
- 284Breen K, Brown A, Burd I, Chai J, Friedman A, Elovitz MA: TLR-4-dependent and -independent mechanisms of fetal brain injury in the setting of preterm birth. Reprod Sci 2012; 19: 839–850.
- 285Watterberg KL, Demers LM, Scott SM, Murphy S: Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996; 97: 210–215.
- 286Yoon BH, Romero R, Kim KS, Park JS, Ki SH, Kim BI, Jun JK: A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1999; 181: 773–779.
- 287Jobe AH, Newnham JP, Willet KE, Moss TJ, Gore Ervin M, Padbury JF, Sly P, Ikegami M: Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol. Am J Respir Crit Care Med 2000; 162: 1656–1661.
- 288Jobe AH, Newnham JP, Willet KE, Sly P, Ervin MG, Bachurski C, Possmayer F, Hallman M, Ikegami M: Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs. Am J Obstet Gynecol 2000; 182: 401–408.
- 289Speer CP: New insights into the pathogenesis of pulmonary inflammation in preterm infants. Biol Neonate 2001; 79: 205–209.
- 290Jobe AH, Ikegami M: Antenatal infection/inflammation and postnatal lung maturation and injury. Respir Res 2001; 2: 27–32.
- 291Willet KE, Kramer BW, Kallapur SG, Ikegami M, Newnham JP, Moss TJ, Sly PD, Jobe AH: Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung. Am J Physiol Lung Cell Mol Physiol 2002; 282: L411–L420.
- 292Speer CP: Inflammation and bronchopulmonary dysplasia. Semin Neonatol 2003; 8: 29–38.
- 293Dammann O, Leviton A, Gappa M, Dammann CE: Lung and brain damage in preterm newborns, and their association with gestational age, prematurity subgroup, infection/inflammation and long term outcome. BJOG 2005; 112(Suppl. 1): 4–9.
- 294Maxwell NC, Davies PL, Kotecha S: Antenatal infection and inflammation: what's new? Curr Opin Infect Dis 2006; 19: 253–258.
- 295Moss TJ, Knox CL, Kallapur SG, Nitsos I, Theodoropoulos C, Newnham JP, Ikegami M, Jobe AH: 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 e121-128.
- 296Lahra MM, Beeby PJ, Jeffery HE: Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics 2009; 123: 1314–1319.
- 297Kramer BW, Kallapur S, Newnham J, Jobe AH: Prenatal inflammation and lung development. Semin Fetal Neonatal Med 2009; 14: 2–7.
- 298Polglase GR, Hillman NH, Ball MK, Kramer BW, Kallapur SG, Jobe AH, Pillow JJ: Lung and systemic inflammation in preterm lambs on continuous positive airway pressure or conventional ventilation. Pediatr Res 2009; 65: 67–71.
- 299Polglase GR, Dalton RG, Nitsos I, Knox CL, Pillow JJ, Jobe AH, Moss TJ, Newnham JP, Kallapur SG: Pulmonary vascular and alveolar development in preterm lambs chronically colonized with Ureaplasma parvum. Am J Physiol Lung Cell Mol Physiol 2010; 299: L232–L241.
- 300Kallapur SG, Kramer BW, Knox CL, Berry CA, Collins JJ, Kemp MW, Nitsos I, Polglase GR, Robinson J, Hillman NH, Newnham JP, Chougnet C, Jobe AH: Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep. J Immunol 2011; 187: 2688–2695.
- 301Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC, Bracken M: Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight. Obstet Gynecol 1989; 73: 576–582.
- 302Smaill F: Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2000; 2: CD000490.
- 303Hall DR, Theron GB, van der Horst W: Significance and treatment of asymptomatic bacteriuria during pregnancy. Int J Gynaecol Obstet 1997; 57: 179–180.
- 304Villar J, Gulmezoglu AM, de Onis M: Nutritional and antimicrobial interventions to prevent preterm birth: an overview of randomized controlled trials. Obstet Gynecol Surv 1998; 53: 575–585.
- 305Smaill F, Vazquez JC: Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2007; 2: CD000490.
- 306Duff P, Lee ML, Hillier SL, Herd LM, Krohn MA, Eschenbach DA: Amoxicillin treatment of bacterial vaginosis during pregnancy. Obstet Gynecol 1991; 77: 431–435.
- 307Lugo-Miro VI, Green M, Mazur L: Comparison of different metronidazole therapeutic regimens for bacterial vaginosis. A meta-analysis. JAMA 1992; 268: 92–95.
- 308Romero R, Sibai B, Caritis S, Paul R, Depp R, Rosen M, Klebanoff M, Sabo V, Evans J, Thom E, Cefalo R, McNellis D: Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial. Am J Obstet Gynecol 1993; 169: 764–774.
- 309Hillier SL, Lipinski C, Briselden AM, Eschenbach DA: Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis. Obstet Gynecol 1993; 81: 963–967.
- 310Livengood CH III, McGregor JA, Soper DE, Newton E, Thomason JL: Bacterial vaginosis: efficacy and safety of intravaginal metronidazole treatment. Am J Obstet Gynecol 1994; 170: 759–764.
- 311Joesoef MR, Hillier SL, Wiknjosastro G, Sumampouw H, Linnan M, Norojono W, Idajadi A, Utomo B: Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm delivery and low birth weight. Am J Obstet Gynecol 1995; 173: 1527–1531.
- 312Cox SM, Bohman VR, Sherman ML, Leveno KJ: Randomized investigation of antimicrobials for the prevention of preterm birth. Am J Obstet Gynecol 1996; 174: 206–210.
- 313McDonald HM, O'Loughlin JA, Vigneswaran R, Jolley PT, Harvey JA, Bof A, McDonald PJ: Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial. Br J Obstet Gynaecol 1997; 104: 1391–1397.
- 314Vermeulen GM, Bruinse HW: Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial. Br J Obstet Gynaecol 1999; 106: 652–657.
- 315Stetzer BP, Mercer BM: Antibiotics and preterm labor. Clin Obstet Gynecol 2000; 43: 809–817.
- 316Carey JC, Klebanoff MA, Hauth JC, Hillier SL, Thom EA, Ernest JM, Heine RP, Nugent RP, Fischer ML, Leveno KJ, Wapner R, Varner M: Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 2000; 342: 534–540.
- 317Kurkinen-Raty M, Vuopala S, Koskela M, Kekki M, Kurki T, Paavonen J, Jouppila P: A randomised controlled trial of vaginal clindamycin for early pregnancy bacterial vaginosis. BJOG 2000; 107: 1427–1432.
- 318Kenyon SL, Taylor DJ, Tarnow-Mordi W: Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group. Lancet 2001; 357: 989–994.
- 319Kekki M, Kurki T, Pelkonen J, Kurkinen-Raty M, Cacciatore B, Paavonen J: Vaginal clindamycin in preventing preterm birth and peripartal infections in asymptomatic women with bacterial vaginosis: a randomized, controlled trial. Obstet Gynecol 2001; 97: 643–648.
- 320Klebanoff MA, Carey JC, Hauth JC, Hillier SL, Nugent RP, Thom EA, Ernest JM, Heine RP, Wapner RJ, Trout W, Moawad A, Leveno KJ, Miodovnik M, Sibai BM, Van Dorsten JP, Dombrowski MP, O'Sullivan MJ, Varner M, Langer O, McNellis D, Roberts JM: Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med 2001; 345: 487–493.
- 321King J, Flenady V: Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst Rev 2002; 12: CD000246.
- 322Andrews WW, Sibai BM, Thom EA, Dudley D, Ernest JM, McNellis D, Leveno KJ, Wapner R, Moawad A, O'Sullivan MJ, Caritis SN, Iams JD, Langer O, Miodovnik M, Dombrowski M: Randomized clinical trial of metronidazole plus erythromycin to prevent spontaneous preterm delivery in fetal fibronectin-positive women. Obstet Gynecol 2003; 101: 847–855.
- 323Guaschino S, Ricci E, Franchi M, Frate GD, Tibaldi C, Santo DD, Ghezzi F, Benedetto C, Seta FD, Parazzini F: Treatment of asymptomatic bacterial vaginosis to prevent pre-term delivery: a randomised trial. Eur J Obstet Gynecol Reprod Biol 2003; 110: 149–152.
- 324Klein LL, Gibbs RS: Use of microbial cultures and antibiotics in the prevention of infection-associated preterm birth. Am J Obstet Gynecol 2004; 190: 1493–1502.
- 325Goldenberg RL, Mwatha A, Read JS, Adeniyi-Jones S, Sinkala M, Msmanga G, Martinson F, Hoffman I, Fawzi W, Valentine M, Emel L, Brown E, Mudenda V, Taha TE: The HPTN 024 Study: the efficacy of antibiotics to prevent chorioamnionitis and preterm birth. Am J Obstet Gynecol 2006; 194: 650–661.
- 326Eschenbach DA: Bacterial vaginosis: resistance, recurrence, and/or reinfection? Clin Infect Dis 2007; 44: 220–221.
- 327Nygren P, Fu R, Freeman M, Bougatsos C, Klebanoff M, Guise JM: Evidence on the benefits and harms of screening and treating pregnant women who are asymptomatic for bacterial vaginosis: an update review for the U.S. Preventive Services Task Force. Ann Intern Med 2008; 148: 220–233.
- 328Macones GA, Parry S, Nelson DB, Strauss JF, Ludmir J, Cohen AW, Stamilio DM, Appleby D, Clothier B, Sammel MD, Jeffcoat M: Treatment of localized periodontal disease in pregnancy does not reduce the occurrence of preterm birth: results from the Periodontal Infections and Prematurity Study (PIPS). Am J Obstet Gynecol 2010; 202: 147 e141-148.
- 329Lamont RF, Nhan-Chang CL, Sobel JD, Workowski K, Conde-Agudelo A, Romero R: Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis. Am J Obstet Gynecol 2011; 205: 177–190.
- 330Brocklehurst P, Gordon A, Heatley E, Milan SJ: Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev 2013; 1: CD000262.
- 331Gulmezoglu AM, Azhar M: Interventions for trichomoniasis in pregnancy. Cochrane Database Syst Rev 2011; 5: CD000220.
- 332Romero R, Chaiworapongsa T, Kuivaniemi H, Tromp G: Bacterial vaginosis, the inflammatory response and the risk of preterm birth: a role for genetic epidemiology in the prevention of preterm birth. Am J Obstet Gynecol 2004; 190: 1509–1519.
- 333Fidel P, Ghezzi F, Romero R, Chaiworapongsa T, Espinoza J, Cutright J, Wolf N, Gomez R: The effect of antibiotic therapy on intrauterine infection-induced preterm parturition in rabbits. J Matern Fetal Neonatal Med 2003; 14: 57–64.
- 334Romero R, Kusanovic JP, Espinoza J, Gotsch F, Nhan-Chang CL, Erez O, Kim CJ, Khalek N, Mittal P, Goncalves LF, Schaudinn C, Hassan SS, Costerton JW: What is amniotic fluid ‘sludge’? Ultrasound Obstet Gynecol 2007; 30: 793–798.
- 335Romero R, Schaudinn C, Kusanovic JP, Gorur A, Gotsch F, Webster P, Nhan-Chang CL, Erez O, Kim CJ, Espinoza J, Goncalves LF, Vaisbuch E, Mazaki-Tovi S, Hassan SS, Costerton JW: Detection of a microbial biofilm in intraamniotic infection. Am J Obstet Gynecol 2008; 198: 135 e131-135.
- 336Donlan RM: Role of biofilms in antimicrobial resistance. ASAIO J 2000; 46: S47–S52.
- 337Stewart PS, Costerton JW: Antibiotic resistance of bacteria in biofilms. Lancet 2001; 358: 135–138.
- 338Stewart PS: Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol 2002; 292: 107–113.
- 339Davies D: Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov 2003; 2: 114–122.
- 340McDuffie RS Jr, Blanton SJ, Shikes RH, Gibbs RS: A rabbit model for bacterially induced preterm pregnancy loss: intervention studies with ampicillin-sulbactam. Am J Obstet Gynecol 1991; 165: 1568–1574.
- 341Gravett MG, Witkin SS, Haluska GJ, Edwards JL, Cook MJ, Novy MJ: An experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol 1994; 171: 1660–1667.
- 342Gravett MG, Sadowsky DW, Witkin SS, Novy MJ: Early but not delayed antibiotic treatment prevents preterm delivery following experimental intraamniotic infection. In Annual Scientific Meeting, Infectious Diseases Society for Obsetrics and Gynecology, 2003.
- 343Grigsby PL, Novy MJ, Sadowsky DW, Morgan TK, Long M, Acosta E, Duffy LB, Waites KB: Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. Am J Obstet Gynecol 2012; 207: 475;e1-475.e14.
- 344Romero R, Scioscia AL, Edberg SC, Hobbins JC: Use of parenteral antibiotic therapy to eradicate bacterial colonization of amniotic fluid in premature rupture of membranes. Obstet Gynecol 1986; 67: 15S–17S.
- 345Romero R, Hagay Z, Nores J, Sepulveda W, Mazor M: Eradication of Ureaplasma urealyticum from the amniotic fluid with transplacental antibiotic treatment. Am J Obstet Gynecol 1992; 166: 618–620.
- 346Mazor M, Chaim W, Horowitz S, Leiberman JR, Glezerman M: Successful treatment of preterm labour by eradication of Ureaplasma urealyticum with erythromycin. Arch Gynecol Obstet 1993; 253: 215–218.
- 347Mazor M, Chaim W, Meirovitz M, Yohay D, Leiberman JR, Glezerman M: Eradication of viridans streptococci from the amniotic cavity by parenteral antibiotic administration. A case report. J Reprod Med 1995; 40: 820–822.
- 348Morency AM, Rallu F, Laferriere C, Bujoldg E: Eradication of intra-amniotic Streptococcus mutans in a woman with a short cervix. J Obstet Gynaecol Can 2006; 28: 898–902.
- 349Hassan S, Romero R, Hendler I, Gomez R, Khalek N, Espinoza J, Nien JK, Berry SM, Bujold E, Camacho N, Sorokin Y: A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med 2006; 34: 13–19.
- 350Mazor M, Chaim W, Maymon E, Hershkowitz R, Romero R: The role of antibiotic therapy in the prevention of prematurity. Clin Perinatol 1998; 25: 659–685, x.
- 351Ovalle A, Romero R, Gomez R, Martinez MA, Nien JK, Ferrand P, Aspillaga C, Figueroa J: Antibiotic administration to patients with preterm labor and intact membranes: is there a beneficial effect in patients with endocervical inflammation? J Matern Fetal Neonatal Med 2006; 19: 453–464.
- 352Weible DR, Randall HW Jr: Evaluation of amniotic fluid in preterm labor with intact membranes. J Reprod Med 1985; 30: 777–780.
- 353Duff P, Kopelman JN: Subclinical intra-amniotic infection in asymptomatic patients with refractory preterm labor. Obstet Gynecol 1987; 69: 756–759.
- 354Harger JH, Meyer MP, Amortegui A, Macpherson TA, Kaplan L, Mueller-Heubach E: Low incidence of positive amnionic fluid cultures in preterm labor at 27-32 weeks in the absence of clinical evidence of chorioamnionitis. Obstet Gynecol 1991; 77: 228–234.
- 355Coultrip LL, Lien JM, Gomez R, Kapernick P, Khoury A, Grossman JH: 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: 901–911.
- 356Yoon BH, Yang SH, Jun JK, Park KH, Kim CJ, Romero R: Maternal blood C-reactive protein, white blood cell count, and temperature in preterm labor: a comparison with amniotic fluid white blood cell count. Obstet Gynecol 1996; 87: 231–237.
- 357Kara 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: 403–406.
- 358Oyarzun E, Gomez R, Rioseco A, Gonzalez P, Gutierrez P, Donoso E, Montiel F: Antibiotic treatment in preterm labor and intact membranes: a randomized, double-blinded, placebo-controlled trial. J Matern Fetal Med 1998; 7: 105–110.
- 359Greci LS, Gilson GJ, Nevils B, Izquierdo LA, Qualls CR, Curet LB: Is amniotic fluid analysis the key to preterm labor? A model using interleukin-6 for predicting rapid delivery. Am J Obstet Gynecol 1998; 179: 172–178.
- 360Garite TJ, Freeman RK: Chorioamnionitis in the preterm gestation. Obstet Gynecol 1982; 59: 539–545.
- 361Zlatnik FJ, Cruikshank DP, Petzold CR, Galask RP: Amniocentesis in the identification of inapparent infection in preterm patients with premature rupture of the membranes. J Reprod Med 1984; 29: 656–660.
- 362Vintzileos AM, Campbell WA, Nochimson DJ, Weinbaum PJ, Escoto DT, Mirochnick MH: Qualitative amniotic fluid volume versus amniocentesis in predicting infection in preterm premature rupture of the membranes. Obstet Gynecol 1986; 67: 579–583.
- 363Feinstein SJ, Vintzileos AM, Lodeiro JG, Campbell WA, Weinbaum PJ, Nochimson DJ: Amniocentesis with premature rupture of membranes. Obstet Gynecol 1986; 68: 147–152.
- 364Gauthier 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: 1092–1095.
- 365Font GE, Gauthier DW, Meyer WJ, Myles TD, Janda W, Bieniarz A: Catalase activity as a predictor of amniotic fluid culture results in preterm labor or premature rupture of membranes. Obstet Gynecol 1995; 85: 656–658.
- 366Averbuch B, Mazor M, Shoham-Vardi I, Chaim W, Vardi H, Horowitz S, Shuster M: Intra-uterine infection in women with preterm premature rupture of membranes: maternal and neonatal characteristics. Eur J Obstet Gynecol Reprod Biol 1995; 62: 25–29.
- 367Carroll SG, Papaioannou S, Ntumazah IL, Philpott-Howard J, Nicolaides KH: Lower genital tract swabs in the prediction of intrauterine infection in preterm prelabour rupture of the membranes. Br J Obstet Gynaecol 1996; 103: 54–59.
- 368Gomez R, Romero R, Nien JK, Chaiworapongsa T, Medina L, Kim YM, Yoon BH, Carstens M, Espinoza J, Iams JD, Gonzalez R: 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: 678–689.
- 369Vaisbuch E, Hassan SS, Mazaki-Tovi S, Nhan-Chang CL, Kusanovic JP, Chaiworapongsa T, Dong Z, Yeo L, Mittal P, Yoon BH, Romero R: 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 e431-438.
- 370Romero R, Shamma F, Avila C, Jimenez C, Callahan R, Nores J, Mazor M, Brekus CA, Hobbins JC: Infection and labor. VI. Prevalence, microbiology, and clinical significance of intraamniotic infection in twin gestations with preterm labor. Am J Obstet Gynecol 1990; 163: 757–761.
- 371Mazor M, Hershkovitz R, Ghezzi F, Maymon E, Horowitz S, Leiberman JR: Intraamniotic infection in patients with preterm labor and twin pregnancies. Acta Obstet Gynecol Scand 1996; 75: 624–627.
- 372Yoon BH, Park KH, Koo JN, Kwon JH, Jun JK, Syn HC, Romero R: Intraamniotic infection of twin pregnancies with preterm labor. Am J Obstet Gynecol 1997; 176: S35.
10.1016/S0002-9378(97)80153-6 Google Scholar
- 373Romero R, Hyun Yoon B, Chaemsaithong P, Cortez J, Park CW, Gonzalez R, Behnke E, Hassan S, Gotsch F, Chaiworapongsa T, Yeo L: Bacteria and Endotoxin in Meconium-Stained Amniotic Fluid at Term: Could Intra-amniotic Infection Cause Meconium Passage? J Matern Fetal Neonatal Med 2013. PMID: 24028637 [Epub ahead of print].
- 374Madan I, Romero R, Kusanovic JP, Mittal P, Chaiworapongsa T, Dong Z, Mazaki-Tovi S, Vaisbuch E, Alpay Savasan Z, Yeo L, Kim CJ, Hassan SS: 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: 275–279.
- 375Gomez R, Romero R, Nien JK, Medina L, Carstens M, Kim YM, Chaiworapongsa T, Espinoza J, Gonzalez R: Idiopathic vaginal bleeding during pregnancy as the only clinical manifestation of intrauterine infection. J Matern Fetal Neonatal Med 2005; 18: 31–37.
- 376Kim SK, Romero R, Kusanovic JP, Erez O, Vaisbuch E, Mazaki-Tovi S, Gotsch F, Mittal P, Chaiworapongsa T, Pacora P, Ogge G, Gomez R, Yoon BH, Yeo L, Lamont RF, Hassan SS: The prognosis of pregnancy conceived despite the presence of an intrauterine device (IUD). J Perinat Med 2010; 38: 45–53.
