Seminars in Fetal & Neonatal Medicine
Volume 17, Issue 1 , Pages 12-19 , February 2012

Intrauterine infection and preterm labor

  • Varkha Agrawal

      Affiliations

    • Department of Obstetrics and Gynecology, NorthShore University HealthSystem, 2650 Ridge Avenue, Evanston, IL 60201, USA
  • ,
  • Emmet Hirsch

      Affiliations

    • Department of Obstetrics and Gynecology, NorthShore University HealthSystem, 2650 Ridge Avenue, Evanston, IL 60201, USA
    • Department of Obstetrics and Gynecology, Pritzker School of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    • Corresponding Author InformationCorresponding author. NorthShore University HealthSystem, Department of Obstetrics and Gynecology, 2650 Ridge Avenue, Evanston, IL 60201, USA. Tel.: +1 847 570 1546; fax: +1 847 570 1846.

References 

  1. Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2007. In: National vital statistics reports: from the centers for disease control and prevention, national center for health statistics. vol. 58:National Vital Statistics System; 2010;p. 1–85
  2. Lockwood CJ. The diagnosis of preterm labor and the prediction of preterm delivery. Clin Obstet Gynecol. 1995;38:675–687
  3. Lamont RF. Infection in the prediction and antibiotics in the prevention of spontaneous preterm labour and preterm birth. BJOG. 2003;110(Suppl. 20):71–75
  4. Romero R, Sirtori M, Oyarzun E, et al. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes. Infect Labor. 1981;161:817–824
  5. Bennett WA, Terrone DA, Rinehart BK, Kassab S, Martin JN, Granger JP. Intrauterine endotoxin infusion in rat pregnancy induces preterm delivery and increases placental prostaglandin F2alpha metabolite levels. Am J Obstet Gynecol. 2000;182:1496–1501
  6. Ilievski V, Hirsch E. Synergy between viral and bacterial toll-like receptors leads to amplification of inflammatory responses and preterm labor in the mouse. Biol Reprod. 2010;83:767–773
  7. Schlafer DH, Yuh B, Foley GL, Elssaser TH, Sadowsky D, Nathanielsz PW. Effect of Salmonella endotoxin administered to the pregnant sheep at 133–142 days gestation on fetal oxygenation, maternal and fetal adrenocorticotropic hormone and cortisol, and maternal plasma tumor necrosis factor alpha concentrations. Biol Reprod. 1994;50:1297–1302
  8. Sadowsky DW, Novy MJ, Witkin SS, Gravett MG. Dexamethasone or interleukin-10 blocks interleukin-1beta-induced uterine contractions in pregnant rhesus monkeys. Am J Obstet Gynecol. 2003;188:252–263
  9. Davies JK, Shikes RH, Sze CI, et al. Histologic inflammation in the maternal and fetal compartments in a rabbit model of acute intra-amniotic infection. Am J Obstet Gynecol. 2000;183:1088–1093
  10. Elovitz MA, Wang Z, Chien EK, Rychlik DF, Phillippe M. A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4. Am J Pathol. 2003;163:2103–2111
  11. Romero R, Mazor M, Tartakovsky B. Systemic administration of interleukin-1 induces preterm parturition in mice. Am J Obstet Gynecol. 1991;165:969–971
  12. Fan YD, Pastorek JG, Miller JM, Mulvey J. Acute pyelonephritis in pregnancy. Am J Perinatol. 1987;4:324–326
  13. Benedetti TJ, Valle R, Ledger WJ. Antepartum pneumonia in pregnancy. Am J Obstet Gynecol. 1982;144:413–417
  14. Xiong X, Buekens P, Fraser WD, Beck J, Offenbacher S. Periodontal disease and adverse pregnancy outcomes: a systematic review. BJOG. 2006;113:135–143
  15. Gomez 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
  16. Gray DJ, Robinson HB, Malone J, Thomson RB. Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum. Prenat Diagn. 1992;12:111–117
  17. Wenstrom KD, Andrews WW, Hauth JC, Goldenberg RL, DuBard MB, Cliver SP. Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery. Am J Obstet Gynecol. 1998;178:546–550
  18. Yoon BH, Oh SY, Romero R, et al. An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery. Am J Obstet Gynecol. 2001;185:1162–1167
  19. Dudley DJ, Collmer D, Mitchell MD, Trautman MS. Inflammatory cytokine mRNA in human gestational tissues: implications for term and preterm labor. J Soc Gynecol Invest. 1996;3:328–335
  20. Caughey AB, Robinson JN, Norwitz ER. Contemporary diagnosis and management of preterm premature rupture of membranes. Rev Obstet Gynecol. 2008;1:11–22
  21. Kumar D, Fung W, Moore RM, et al. Proinflammatory cytokines found in amniotic fluid induce collagen remodeling, apoptosis, and biophysical weakening of cultured human fetal membranes. Biol Reprod. 2006;74:29–34
  22. Romero 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
  23. Romero R, Gonzalez R, Sepulveda W, et al. Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance. Am J Obstet Gynecol. 1992;167:1086–1091
  24. Hassan S, Romero R, Hendler I, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med. 2006;34:13–19
  25. DiGiulio DB, Romero R, Amogan HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PloS One. 2008;3:e3056
  26. Romero R, Mazor M, Morrotti R, et al. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term. Infect Labor. 1992;166:129–133
  27. Koi H, Zhang J, Parry S. The mechanisms of placental viral infection. Ann NY Acad Sci. 2001;943:148–156
  28. Baschat 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 Maternal Fetal Neonat Med. 2003;13:381–384
  29. Reddick KLB, Jhaveri R, Gandhi M, James AH, Swamy GK. Pregnancy outcomes associated with viral hepatitis. J Viral Hepatitis. 2011;18:e394–e398
  30. Ilievski V, Lu SJ, Hirsch E. Activation of toll-like receptors 2 or 3 and preterm delivery in the mouse. Reprod Sci. 2007;14:315–320
  31. Koga K, Cardenas I, Aldo P, et al. Activation of TLR3 in the trophoblast is associated with preterm delivery. Am J Reprod Immunol. 2009;61:196–212
  32. Lee Y, Allport V, Sykes A, Lindstrom T, Slater D, Bennett P. The effects of labour and of interleukin 1 beta upon the expression of nuclear factor kappa B related proteins in human amnion. Mol Hum Reprod. 2003;9:213–218
  33. Patel FA, Challis JR. Prostaglandins and uterine activity. Front Horm Res. 2001;27:31–56
  34. Phillippe M, Elovitz M, Saunders T. Thrombin-stimulated uterine contractions in the pregnant and nonpregnant rat. J Soc Gynecol Invest. 2001;8:260–265
  35. Girardi G, Bulla R, Salmon JE, Tedesco F. The complement system in the pathophysiology of pregnancy. Mol Immunol. 2006;43:68–77
  36. Lynch AM, Gibbs RS, Murphy JR, Giclas PC, Salmon JE, Holers VM. Early elevations of the complement activation fragment C3a and adverse pregnancy outcomes. Obstet Gynecol. 2011;117:75–83
  37. Grigsby PL, Hirst JJ, Scheerlinck JP, Phillips DJ, Jenkin G. Fetal responses to maternal and intra-amniotic lipopolysaccharide administration in sheep. Biol Reprod. 2003;68:1695–1702
  38. Dudley DJ, Chen CL, Branch DW, Hammond E, Mitchell MD. A murine model of preterm labor: inflammatory mediators regulate the production of prostaglandin E2 and interleukin-6 by murine decidua. Biol Reprod. 1993;48:33–39
  39. Fidel PL, Romero R, Wolf N, et al. Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice. Am J Obstet Gynecol. 1994;170:1467–1475
  40. Robertson SA, Skinner RJ, Care AS. Essential role for IL-10 in resistance to lipopolysaccharide-induced preterm labor in mice. J Immunol. 2006;177:4888–4896
  41. Terrone DA, Rinehart BK, Granger JP, Barrilleaux PS, Martin JN, Bennett WA. Interleukin-10 administration and bacterial endotoxin-induced preterm birth in a rat model. Obstet Gynecol. 2001;98:476–480
  42. Moura E, Mattar R, de Souza E, Torloni MR, Gonçalves-Primo A, Daher S. Inflammatory cytokine gene polymorphisms and spontaneous preterm birth. J Reprod Immunol. 2009;80:115–121
  43. Lorenz E, Hallman M, Marttila R, Haataja R, Schwartz DA. Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population. Pediatr Res. 2002;52:373–376
  44. Hollegaard MV, Grove J, Thorsen P, et al. Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth. Acta Obstet Gynecol Scand. 2008;87:1285–1290
  45. Ferrand PE, Parry S, Sammel M, et al. A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans. Mol Hum Reprod. 2002;8:494–501
  46. Fujimoto T, Parry S, Urbanek M, et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter influences amnion cell MMP-1 expression and risk for preterm premature rupture of the fetal membranes. J Biol Chem. 2002;277:6296–6302
  47. Espinoza J, Erez O, Romero R. Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery. Am J Obstet Gynecol. 2006;194:630–637
  48. van den Broek NR, White SA, Goodall M, et al. The APPLe study: a randomized, community-based, placebo-controlled trial of azithromycin for the prevention of preterm birth, with meta-analysis. PLoS Med. 2009;6:e1000191
  49. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188:419–424
  50. Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011;38:18–31
  51. Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348:2379–2385
  52. Elovitz M, Wang Z. Medroxyprogesterone acetate, but not progesterone, protects against inflammation-induced parturition and intrauterine fetal demise. Am J Obstet Gynecol. 2004;190:693–701
  53. Zarember KA, Godowski PJ. Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol. 2002;168:554–561
  54. Holmlund U, Cebers G, Dahlfors AR, et al. Expression and regulation of the pattern recognition receptors Toll-like receptor-2 and Toll-like receptor-4 in the human placenta. Immunol. 2002;107:145–151
  55. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunol. 2010;11:373–384
  56. Mor G. Inflammation and pregnancy: the role of toll-like receptors in trophoblast-immune interaction. Ann NY Acad Sci. 2008;1127:121–128
  57. Mor G, Romero R, Aldo PB, Abrahams VM. Is the trophoblast an immune regulator? The role of Toll-like receptors during pregnancy. Crit Rev Immunol. 2005;25:375–388
  58. Gonzalez JM, Xu H, Ofori E, Elovitz MA. Toll-like receptors in the uterus, cervix, and placenta: is pregnancy an immunosuppressed state?. Am J Obstet Gynecol. 2007;197(296):e291–e296
  59. Equils O, Moffatt-Blue C, Ishikawa TO, Simmons CF, Ilievski V, Hirsch E. Pretreatment with pancaspase inhibitor (Z-VAD-FMK) delays but does not prevent intraperitoneal heat-killed group B Streptococcus-induced preterm delivery in a pregnant mouse model. Infect Dis Obstet Gynecol. 2009;2009:749432
  60. Kim YM, Romero R, Chaiworapongsa T, et al. Toll-like receptor-2 and -4 in the chorioamniotic membranes in spontaneous labor at term and in preterm parturition that are associated with chorioamnionitis. Am J Obstet Gynecol. 2004;191:1346–1355
  61. Abrahams VM, Aldo PB, Murphy SP, et al. TLR6 modulates first trimester trophoblast responses to peptidoglycan. J Immunol. 2008;180:6035–6043
  62. Wang H, Hirsch E. Bacterially-induced preterm labor and regulation of prostaglandin-metabolizing enzyme expression in mice: the role of toll-like receptor 4. Biol Reprod. 2003;69:1957–1963
  63. Li L, Kang J, Lei W. Role of Toll-like receptor 4 in inflammation-induced preterm delivery. Mol Hum Reprod. 2010;16:267–272
  64. Adams Waldorf KM, Persing D, Novy MJ, Sadowsky DW, Gravett MG. Pretreatment with Toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys. Reprod Sci. 2008;15:121–127
  65. Pawelczyk E, Nowicki BJ, Izban MG, et al. Spontaneous preterm labor is associated with an increase in the proinflammatory signal transducer TLR4 receptor on maternal blood monocytes. BMC Pregn Childbirth. 2010;10:66
  66. Thaxton JE, Romero R, Sharma S. TLR9 activation coupled to IL-10 deficiency induces adverse pregnancy outcomes. J Immunol. 2009;183:1144–1154
  67. Cardenas I, Means RE, Aldo P, et al. Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J Immunol. 2010;185:1248–1257
  68. Cardenas I, Mor G, Aldo P, et al. Placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis. Am J Reprod Immunol. 2011;65:110–117
  69. Farina L, Winkelman C. A review of the role of proinflammatory cytokines in labor and noninfectious preterm labor. Biol Res Nurs. 2005;6:230–238
  70. Menon R, Fortunato SJ. Fetal membrane inflammatory cytokines: a switching mechanism between the preterm premature rupture of the membranes and preterm labor pathways. J Perinat Med. 2004;32:391–399
  71. Figueroa R, Garry D, Elimian A, Patel K, Sehgal PB, Tejani N. Evaluation of amniotic fluid cytokines in preterm labor and intact membranes. J Maternal Fetal Neonat Med. 2005;18:241–247
  72. Mattsby-Baltzer I, Platz-Christensen JJ, Hosseini N, Rosen P. IL-1beta, IL-6, TNFalpha, fetal fibronectin, and endotoxin in the lower genital tract of pregnant women with bacterial vaginosis. Acta Obstet Gynecol Scand. 1998;77:701–706
  73. Rizzo G, Capponi A, Rinaldo D, Tedeschi D, Arduini D, Romanini C. Interleukin-6 concentrations in cervical secretions identify microbial invasion of the amniotic cavity in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 1996;175:812–817
  74. Tanaka Y, Narahara H, Takai N, Yoshimatsu J, Anai T, Miyakawa I. Interleukin-1beta and interleukin-8 in cervicovaginal fluid during pregnancy. Am J Obstet Gynecol. 1998;179:644–649
  75. Jun JK, Yoon BH, Romero R, et al. Interleukin 6 determinations in cervical fluid have diagnostic and prognostic value in preterm premature rupture of membranes. Am J Obstet Gynecol. 2000;183:868–873
  76. Sadowsky DW, Adams KM, Gravett MG, Witkin SS, Novy MJ. Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model. Am J Obstet Gynecol. 2006;195:1578–1589
  77. Hirsch E, Filipovich Y, Mahendroo M. Signaling via the type I IL-1 and TNF receptors is necessary for bacterially induced preterm labor in a murine model. Am J Obstet Gynecol. 2006;194:1334–1340
  78. Gross G, Imamura T, Vogt SK, et al. Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse. Am J Physiol Regul Integrat Comp Physiol. 2000;278:R1415–R1423
  79. Sato TA, Gupta DK, Keelan JA, Marvin KW, Mitchell MD. Cytosolic phospholipase A(2)and 15-hydroxyprostaglandin dehydrogenase mRNA expression in murine uterine and gestational tissues during late pregnancy. Prostagl Leukotr Essent Fatty Acids. 2001;64:247–251
  80. Luo G, Abrahams VM, Tadesse S, et al. Progesterone inhibits basal and TNF-alpha-induced apoptosis in fetal membranes: a novel mechanism to explain progesterone-mediated prevention of preterm birth. Reprod Sci. 2010;17:532–539
  81. Fang X, Wong S, Mitchell BF. Messenger RNA for progesterone receptor isoforms in the late-gestation rat uterus. Am J Physiol. 2002;283:E1167–E1172
  82. Shields AD, Wright J, Paonessa DJ, et al. Progesterone modulation of inflammatory cytokine production in a fetoplacental artery explant model. Am J Obstet Gynecol. 2005;193:1144–1148
  83. Challis JR, Sloboda DM, Alfaidy N. Prostaglandins and mechanisms of preterm birth. Reproduction. 2002;124:1–17
  84. Yallampalli C, Dong YL, Gangula PR, Fang L. Role and regulation of nitric oxide in the uterus during pregnancy and parturition. J Soc Gynecol Invest. 1998;5:58–67
  85. Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Mental Retard Dev Disabil Res Rev. 2002;8:3–13
  86. Tiboni G, Del Corso A, Marotta RK. Progestational agents prevent preterm birth induced by a nitric oxide synthesis inhibitor in the mouse. In Vivo. 2008;22:447–450
  87. Woods JR, Plessinger MA, Miller RK. Vitamins C and E: missing links in preventing preterm premature rupture of membranes?. Am J Obstet Gynecol. 2001;185:5–10
  88. Nassi N, Ponziani V, Becatti M, Galvan P, Donzelli G. Anti-oxidant enzymes and related elements in term and preterm newborns. Pediatr Int. 2009;51:183–187
  89. Kawano Y, Narahara H, Johnston JM. Inhibitory effect of interleukin-8 on the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages. J Soc Gynecol Invest. 1999;6:328–332
  90. Matsubara T, Yasuda K, Johnston JM, et al. Platelet-activating factor (PAF) and PAF acetylhydrolase activity in rat uterus and placenta during the late stages of pregnancy. Biol Reprod. 1997;56:885–890
  91. Silver RK, Caplan MS, Kelly AM. Amniotic fluid platelet-activating factor (PAF) is elevated in patients with tocolytic failure and preterm delivery. Prostaglandins. 1992;43:181–187
  92. Garcia-Verdugo I, Tanfin Z, Dallot E, Leroy MJ, Breuiller-Fouche M. Surfactant protein A signaling pathways in human uterine smooth muscle cells. Biol Reprod. 2008;79:348–355
  93. Condon JC, Jeyasuria P, Faust JM, Mendelson CR. Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition. Proc Natl Acad Sci USA. 2004;101:4978–4983
  94. Jiang D, Liang J, Fan J, et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nature Med. 2005;11:1173–1179
  95. El Maradny E, Kanayama N, Kobayashi H, et al. The role of hyaluronic acid as a mediator and regulator of cervical ripening. Hum Reprod. 1997;12:1080–1088

PII: S1744-165X(11)00097-7

doi: 10.1016/j.siny.2011.09.001

Seminars in Fetal & Neonatal Medicine
Volume 17, Issue 1 , Pages 12-19 , February 2012