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Preterm birth due to maternal infection: causative pathogens and modes of prevention

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Abstract

Preterm birth represents a major problem for modern obstetrics due to its increasing frequency and the accompanying socioeconomic impact. Although several maternal characteristics related to preterm birth have been identified, the etiology in most cases remains inadequately understood. Various microorganisms have been linked to the pathogenesis of preterm birth. Microbes may reach the amniotic cavity and fetus by ascending from the vagina and cervix, by hematogenous distribution through the placenta, by migration from the abdominal cavity through the fallopian tubes, or through invasive medical procedures. Organisms commonly cultured from the amniotic cavity following preterm delivery include Ureaplasma urealyticum, Mycoplasma hominis, Bacteroides spp., Gardnerella vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and group B hemolytic streptococci. Several trials have examined the effect of antibiotic administration to patients with preterm labor and intact membranes, preterm premature rupture of the membranes, genital mycoplasmal infection, asymptomatic bacteriuria, and bacterial vaginosis. The results of such studies, which were variable and often conflicting, are discussed here.

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References

  1. World Health Organization (1970) The prevention of perinatal mortality and morbidity. WHO technical report series (report 457). WHO, Geneva

    Google Scholar 

  2. Friese K (2003) The role of infection in preterm labor. BJOG 110 (Suppl 20):52–54

    PubMed  CAS  Google Scholar 

  3. McCormick MC (1985) The contribution of low birth-weight to infant mortality and childhood morbidity. N Engl J Med 312:82–90

    Article  PubMed  CAS  Google Scholar 

  4. Hack M, Fanaroff AA (1993) Outcomes of extremely immature children—a perinatal dilemma. N Engl J Med 329:1649–1650

    Article  PubMed  CAS  Google Scholar 

  5. Offenbacher S (2004) Maternal periodontal infections. Prematurity and growth restriction. Clin Obstet Gynecol 47:808–821

    Article  PubMed  Google Scholar 

  6. Hollier LM (2005) Preventing preterm birth. What works and what doesn’t. Obstet Gynecol 60:124–131

    Google Scholar 

  7. Martin JA, Hamilton BE, Sutton PD et al (2003) Births: final data for 2002. National vital statistics reports, vol. 52 (10). National Center for Health, Hyattsville, MD

    Google Scholar 

  8. Adams KM, Eschenbach DA (2004) The genetic contribution towards preterm delivery. Semin Fetal Neonat Med 9:445–452

    Article  Google Scholar 

  9. Arntzen KJ, Kjollesdal AM, Halgunset J et al (1998) TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labour. J Perinat Med 26:17–26

    PubMed  CAS  Google Scholar 

  10. Wilson AG, de Vries N, Pociot F et al (1993) An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med 177:557–560

    Article  PubMed  CAS  Google Scholar 

  11. Aidoo M, McElroy PD, Kolczak MS et al (2001) Tumor necrosis factor–alpha promoter variant 2 (TNF2) is associated with preterm delivery, infant mortality, and malaria morbidity in western Kenya: Asembo bay cohort project IX. Genet Epidemiol 21:202–211

    Article  Google Scholar 

  12. Roberts AK, Monzon-Bordonaba F, Van Deerlin PJ et al (1999) Association of polymorphism within the promoter of the tumor necrosis factor alpha gene with increased risk of preterm premature rupture of the fetal membranes. Am J Obstet Gynecol 180:1297–1302

    Article  PubMed  CAS  Google Scholar 

  13. Averbuch B, Mazor M, Shoham-Vardi I et al (1995) Intra-uterine infection in women with preterm premature rupture of membranes: maternal and neonatal characteristics. Eur J Obstet Gynecol Reprod Biol 62:25–29

    Article  PubMed  CAS  Google Scholar 

  14. Benedetti TJ, Valle R, Ledger WJ (1982) Antepartum pneumonia in pregnancy. Am J Obstet Gynecol 144:413–417

    PubMed  CAS  Google Scholar 

  15. Madinger NE, Greenpspoon JS, Ellrodt AG (1989) Pneumonia during pregnancy: has modern technology improved maternal and fetal outcome? Am J Obstet Gynecol 161:657–662

    PubMed  CAS  Google Scholar 

  16. Cunningham FG, Morris GB, Mickal A (1973) Acute pyelonephritis of pregnancy: a clinical review. Obstet Gynecol 42:112–117

    PubMed  CAS  Google Scholar 

  17. Gilles HM, Lawson JB, Sibellas M et al (1969) Malaria, anemia and pregnancy. Ann Trop Med Parasitol 63:245–263

    PubMed  CAS  Google Scholar 

  18. Heard N, Jordan T (1981) An investigation of malaria during pregnancy in Zimbabwe. Centr Afr J Med 27:62–68

    CAS  Google Scholar 

  19. Rigall F, Salkind G, Spellacy W (1974) Typhoid fever complicating pregnancy. Obstet Gynecol 44:117–121

    Google Scholar 

  20. Yost NP, Cox SM (2000) Infection and preterm labor. Clin Obstet Gynecol 43:759–767

    Article  PubMed  CAS  Google Scholar 

  21. Goldenberg RL, Hauth JC, Andrews WW (2000) Intra-uterine infection and preterm delivery. N Engl J Med 342:1500–1507

    Article  Google Scholar 

  22. McGregor JA, French JI (2000) Bacterial vaginosis in pregnancy. Obstet Gynecol Surv 55(Suppl 1):S1–S19

    Article  PubMed  CAS  Google Scholar 

  23. Romero R, Espinoza J, Chaiworapongsa T, Kalache K (2002) Infection and prematurity and the role of preventing strategies. Semin Neonatol 7:259–274

    PubMed  Google Scholar 

  24. Gibbs RS, Romero R, Hillier SL et al (1992) A review of premature birth and subclinical infection. Am J Obstet Gynecol 166:1515–1528

    PubMed  CAS  Google Scholar 

  25. Hauth JC, Andrews WW, Goldenberg RL (1998) Infection-related risk factors predictive of spontaneous labor and birth. Prenat Neonatal Med 3:86–90

    Google Scholar 

  26. Krohn MA, Hillier SL, Nugent RP et al (1995) The genital flora of women with intraamniotic infection. J Infect Dis 171:1475–1480

    PubMed  CAS  Google Scholar 

  27. Hillier SL, Martins J, Krohn M et al (1988) A case control study of chorioamniotic infection and histologic chorioamnionitis in prematurity. N Engl J Med 319:972–978

    Article  PubMed  CAS  Google Scholar 

  28. Andrews WW, Goldenberg RL, Hauth JC (1995) Preterm labor: emerging role of genital tract infections. Infect Agents Dis 4:196–211

    PubMed  CAS  Google Scholar 

  29. Cassell G (1999) Ureaplasma infection. In: Hitchcock PJ, MacKay HT, Wasserheit JN, Binder R (eds) Sexually transmitted diseases and adverse outcomes of pregnancy. ASM, Washington DC, pp 175–193

    Google Scholar 

  30. Berg TG, Philpot KL, Welsh MS et al (1999) Ureaplasma/Mycoplasma–infected amniotic fluid: pregnancy outcome in treated and nontreated patients. J Perinatol 19:275–277

    Article  PubMed  CAS  Google Scholar 

  31. Kafetzis DA, Skevaki CL, Skouteri V et al (2004) Maternal genital colonization with Ureaplasma urealyticum promotes preterm delivery: association of the respiratory colonization of premature infants with chronic lung disease and increased mortality. Clin Infect Dis 39:1113–1122

    Article  PubMed  Google Scholar 

  32. Horowitz S, Mazor M, Romero R et al (1995) Infection of the amniotic cavity with Ureaplasma urealyticum in the midtrimester of pregnancy. J Reprod Med 40:375–379

    PubMed  CAS  Google Scholar 

  33. Gray DJ, Robinson HB, Malone J et al (1992) Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum. Prenat Diagn 12:111–117

    Article  PubMed  CAS  Google Scholar 

  34. Nugent RP, Krohn MA, Hillier SL (1991) Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J Clin Microbiol 29:297–301

    PubMed  CAS  Google Scholar 

  35. Amsel R, Totten PA, Spiegel CA et al (1983) Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med 74:14–22

    Article  PubMed  CAS  Google Scholar 

  36. Hillier SL, Nugent RP, Eschenbach DA et al (1995) Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 333:1737–1742

    Article  PubMed  CAS  Google Scholar 

  37. Meis PJ, Goldenberg RL, Mercer B et al (1995) The Preterm Prediction Study: significance of vaginal infections. National Institute of Child Health and Human Development Network of Maternal–Fetal Medicine Units. Am J Obstet Gynecol 173:1231–1235

    Article  PubMed  CAS  Google Scholar 

  38. Flynn CA, Helwig AL, Meurer LN (1999) Bacterial vaginosis in pregnancy and the risk of prematurity: a meta-analysis. J Fam Pract 48:885–992

    PubMed  CAS  Google Scholar 

  39. Garland SM, Kelly N, Ugoni AM (2000) Is antenatal group B streptococcal carriage a predictor of adverse obstetric outcome? Infect Dis Obstet Gynecol 8:138–142

    Article  PubMed  CAS  Google Scholar 

  40. Cotch MF, Pastorek JG, Nugent RP et al (1997) Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis 24:353–360

    Article  PubMed  CAS  Google Scholar 

  41. Goldenberg RL, Andrews WW, Yuan AC et al (1997) Sexually transmitted diseases and adverse outcomes of pregnancy. Clin Perinatol 24:23–41

    PubMed  CAS  Google Scholar 

  42. Sweet R, Landers DV, Walker C, Schachter J (1987) Chlamydia trachomatis infection and pregnancy outcome. Am J Obstet Gynecol 156:824–833

    PubMed  CAS  Google Scholar 

  43. Andrews WW, for the NICHD MFMU Network (1997) The preterm prediction study: association of mid-trimester genital Chlamydia infection and subsequent spontaneous preterm birth. Am J Obstet Gynecol (Abstract 176, issue 1, part 2):S52

  44. Jeffcoat MK, Geurs NC, Reddy MS et al (2001) Periodontal infection and preterm birth: results of a prospective study. J Am Dent Assoc 132:875–880

    PubMed  CAS  Google Scholar 

  45. Offenbacher S, Lieff S, Boggess KA et al (2001) Maternal periodontitis and prematurity. Part I: obstetric outcome of prematurity and growth restriction. Ann Periodontol 6:164–174

    Article  PubMed  CAS  Google Scholar 

  46. Lopez NJ, Smith PC, Giuterrez J (2002) Higher risk of preterm birth weight in women with periodontal disease. J Dent Res 81:58–63

    PubMed  CAS  Google Scholar 

  47. Offenbacher S, Katz V, Fertik G et al (1996) Periodontal infection as a possible risk factor for preterm low birth weight. J Periodontol 67(Suppl 10):1103–1113

    PubMed  CAS  Google Scholar 

  48. Davenport ES, Williams CE, Sterne JA et al (2002) Maternal periodontal disease and preterm low birth weight: case-control study. J Dent Res 81:313–318

    Article  PubMed  CAS  Google Scholar 

  49. Madianos PN, Lieff S, Offenbacher S et al (2001) Maternal periodontitis and prematurity: Part 2: maternal infection and fetal exposure. Ann Periodontol 30:26–31

    Google Scholar 

  50. Kenyon SL, Taylor DJ, Tarnow-Mordi W (2001) Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the Oracle I randomized trial. ORACLE Collaborative Group. Lancet 357:979–988

    Article  PubMed  CAS  Google Scholar 

  51. Kenyon SL, Taylor DJ, Tarnow-Mordi W (2001) Broad-spectrum antibiotics for spontaneous preterm labour: the Oracle II randomized trial. ORACLE Collaborative Group. Lancet 357:989–994

    Article  PubMed  CAS  Google Scholar 

  52. Lamont RF, Taylor-Robinson D, Hay PE (2001) Antibiotics for adverse outcomes of pregnancy. Lancet 358:1728

    Article  PubMed  CAS  Google Scholar 

  53. Romero R, Oyarzun E, Mazor M et al (1989) Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight. Obstet Gynecol 73:576–582

    PubMed  CAS  Google Scholar 

  54. Gravett MG, Hummel D, Eschenbach DA, Holmes KK (1986) Preterm labour associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol 67:229–237

    Article  PubMed  CAS  Google Scholar 

  55. Hauth JC, Goldenberg RL, Andrews WW et al (1995) Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med 333:1732–1736

    Article  PubMed  CAS  Google Scholar 

  56. McDonald HM, O’ Loughlin JA, Vigneswaran R et al (1997) Impact of metronidazole therapy on preterm in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomized, placebo controlled trial. Br J Obstet Gynaecol 104:1391–1397

    PubMed  CAS  Google Scholar 

  57. Morales WJ, Schorr S, Albritton J (1994) Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am J Obstet Gynecol 171:345–349

    PubMed  CAS  Google Scholar 

  58. Carey JC, Klebanoff MA, Hauth JC et al (2000) 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 342:534–540

    Article  PubMed  CAS  Google Scholar 

  59. Ugwumandu A, Manyonda I, Reid F et al (2003) Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomized controlled trial. Lancet 361:983–988

    Article  CAS  Google Scholar 

  60. Joesoef MR, Hillier SL, Wiknjosastro G et al (1995) Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm delivery and low birth weight. Am J Obstet Gynecol 173:1527–1531

    Article  PubMed  CAS  Google Scholar 

  61. Rosenstein IJ, Morgan DJ, Lamont RF et al (2000) Effect of intravaginal clindamycin cream on pregnancy outcome and on abnormal vaginal microbial flora of pregnant women. Infect Dis Obstet Gynecol 8:158–165

    Article  PubMed  CAS  Google Scholar 

  62. Hauth JC, Cliver S, Hodgkins P et al (2001) Mid-trimester metronidazole and azithromycin did not prevent preterm birth in women at increased risk: a double-blind trial. Am J Obstet Gynecol 185(Suppl 1):S86

    Article  Google Scholar 

  63. Eschenbach DA, Nugent RP, Rao AV et al (1991) A randomized placebo-controlled trial of erythromycin for the treatment of Ureaplasma urealyticum to prevent premature delivery. The Vaginal Infections and Prematurity Study Group. Am J Obstet Gynecol 164:734–742

    PubMed  CAS  Google Scholar 

  64. Klein LL, Gibbs RS (2004) Use of microbial cultures and antibiotics in the prevention of infection-associated preterm birth. Am J Obstet Gynecol 190:1493–1502

    Article  PubMed  CAS  Google Scholar 

  65. Burtin P, Taddio A, Ariburnu O et al (1995) Fetus–placenta–newborn: safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol 172:525–529

    Article  PubMed  CAS  Google Scholar 

  66. Klebanoff MA, Carey JC, Hauth JC et al (2001) Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med 345:487–493

    Article  PubMed  CAS  Google Scholar 

  67. Carey JC, Klebanoff MA (2005) Is a change in the vaginal flora associated with an increased risk of preterm birth? Am J Obstet Gynecol 192:1341–1347

    Article  PubMed  Google Scholar 

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Pararas, M.V., Skevaki, C.L. & Kafetzis, D.A. Preterm birth due to maternal infection: causative pathogens and modes of prevention. Eur J Clin Microbiol Infect Dis 25, 562–569 (2006). https://doi.org/10.1007/s10096-006-0190-3

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