The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term

Roberto Romero, Sonia S Hassan, Pawel Gajer, Adi L Tarca, Douglas W Fadrosh, Janine Bieda, Piya Chaemsaithong, Jezid Miranda, Tinnakorn Chaiworapongsa, Jacques Ravel, Roberto Romero, Sonia S Hassan, Pawel Gajer, Adi L Tarca, Douglas W Fadrosh, Janine Bieda, Piya Chaemsaithong, Jezid Miranda, Tinnakorn Chaiworapongsa, Jacques Ravel

Abstract

Background: This study was undertaken to determine whether the vaginal microbiota of pregnant women who subsequently had a spontaneous preterm delivery is different from that of women who had a term delivery.

Results: This was a nested case-control study of pregnant women who had a term delivery (controls) and those who had a spontaneous preterm delivery before 34 weeks of gestation (cases). Samples of vaginal fluid were collected longitudinally and stored at -70°C until assayed. A microbial survey using pyrosequencing of V1-V3 regions of 16S rRNA genes was performed. We tested the hypothesis of whether the relative abundance of individual microbial species (phylotypes) was different between women who had a term versus preterm delivery. A suite of bioinformatic and statistical tools, including linear mixed effects models and generalized estimating equations, was used. We show that: 1) the composition of the vaginal microbiota during normal pregnancy changed as a function of gestational age, with an increase in the relative abundance of four Lactobacillus spp., and decreased in anaerobe or strict-anaerobe microbial species as pregnancy progressed; 2) no bacterial taxa differed in relative abundance between women who had a spontaneous preterm delivery and those who delivered at term; and 3) no differences in the frequency of the vaginal community state types (CST I, III, IV-B) between women who delivered at term and those who delivered preterm were detected.

Conclusions: The bacterial taxa composition and abundance of vaginal microbial communities, characterized with 16S rRNA gene sequence-based techniques, were not different in pregnant women who subsequently delivered a preterm neonate versus those who delivered at term.

Keywords: Histologic chorioamnionitis; Infection-induced preterm delivery; Prematurity; Vaginal flora; Vaginal microbiome.

Figures

Figure 1
Figure 1
Heatmap of microbial taxa relative abundance identified in the vaginal microbiota of women who delivered at term and women who delivered preterm. Ward linkage clustering of samples based on the composition and relative abundance of the 25 most abundant species in the vaginal microbiota that define community state types is shown above the heatmap.
Figure 2
Figure 2
Profiles of community state types for women who delivered at term and women who delivered preterm as a function of the gestational age. Each sample in the longitudinal series was assigned to community state types as defined in Figure 1 and is indicated by a rectangle colored according to the legend shown above. Time of delivery is depicted by a light blue circle.

References

    1. World Health Organization. Born Too Soon: The Global Action Report in Preterm Birth. Geneva; 2012.
    1. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menon R, Van Look PF. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010;88:31–38. doi: 10.2471/BLT.08.062554.
    1. Premature Birth. [ ]
    1. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2012. Natl Vital Stat Rep. 2012;62:1–20.
    1. Goldenberg RL, McClure EM. In: Preterm Birth: Prevention and Management. Berguella V, editor. Oxford: Willey-Blackwell; 2010. The epidemiology of preterm birth; pp. 22–38.
    1. Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med. 2010;362:529–535. doi: 10.1056/NEJMra0904308.
    1. Blencowe 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. doi: 10.1016/S0140-6736(12)60820-4.
    1. Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B. Annual summary of vital statistics: 2010–2011. Pediatrics. 2013;131:548–558. doi: 10.1542/peds.2012-3769.
    1. Iams JD, Romero R, Culhane JF, Goldenberg RL. Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet. 2008;371:164–175. doi: 10.1016/S0140-6736(08)60108-7.
    1. Romero R, Espinoza J, Chaiworapongsa T, Kalache K. Infection and prematurity and the role of preventive strategies. Semin Neonatol. 2002;7:259–274. doi: 10.1016/S1084-2756(02)90121-1.
    1. Romero 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.
    1. Behrman RE, Butler AS. In: Preterm Birth: Causes, Consequences and Prevention. Policy CoUPBaAHOBoHS, Behrman RE, Butler AS, editor. Washington, D.C: National Academies Press; 2007. Social costs of preterm birth; pp. 398–432.
    1. Russell RB, Green NS, Steiner CA, Meikle S, Howse JL, Poschman K, Dias T, Potetz L, Davidoff MJ, Damus K, Petrini JR. Cost of hospitalization for preterm and low birth weight infants in the United States. Pediatrics. 2007;120:e1–9. doi: 10.1542/peds.2006-2386.
    1. March of Dimes. The Impact of Premature Birth on Society. Available at: .
    1. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371:75–84. doi: 10.1016/S0140-6736(08)60074-4.
    1. Romero R, Mazor M, Munoz H, Gomez R, Galasso M, Sherer DM. The preterm labor syndrome. Ann N Y Acad Sci. 1994;734:414–429. doi: 10.1111/j.1749-6632.1994.tb21771.x.
    1. Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, Chaiworapongsa T, Mazor M. The preterm parturition syndrome. BLOG. 2006;113(Suppl 3):17–42.
    1. Romero 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.
    1. Romero 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. doi: 10.1016/0002-9378(89)90409-2.
    1. Romero 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.
    1. Bobitt JR, Hayslip CC, Damato JD. Amniotic fluid infection as determined by transabdominal amniocentesis in patients with intact membranes in premature labor. Am J Obstet Gynecol. 1981;140:947–952.
    1. Wahbeh CJ, Hill GB, Eden RD, Gall SA. Intra-amniotic bacterial colonization in premature labor. Am J Obstet Gynecol. 1984;148:739–743. doi: 10.1016/0002-9378(84)90558-1.
    1. Gravett MG, Hummel D, Eschenbach DA, Holmes KK. Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol. 1986;67:229–237. doi: 10.1097/00006250-198602000-00013.
    1. Leigh J, Garite TJ. Amniocentesis and the management of premature labor. Obstet Gynecol. 1986;67:500–506.
    1. Bruner JP, Elliott JP, Kilbride HW, Garite TJ, Knox GE. Candida chorioamnionitis diagnosed by amniocentesis with subsequent fetal infection. Am J Perinatol. 1986;3:213–218. doi: 10.1055/s-2007-999870.
    1. Romero R, Mazor M. Infection and preterm labor. Clin Obstet Gynecol. 1988;31:553–584. doi: 10.1097/00003081-198809000-00006.
    1. Romero 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. doi: 10.1016/S0002-9378(88)80030-9.
    1. Silver HM, Sperling RS, St Clair PJ, Gibbs RS. Evidence relating bacterial vaginosis to intraamniotic infection. Am J Obstet Gynecol. 1989;161:808–812. doi: 10.1016/0002-9378(89)90406-7.
    1. Watts DH, Krohn MA, Hillier SL, Eschenbach DA. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol. 1992;79:351–357. doi: 10.1097/00006250-199203000-00005.
    1. Romero R, Salafia CM, Athanassiadis AP, Hanaoka S, Mazor M, Sepulveda W, Bracken MB. The relationship between acute inflammatory lesions of the preterm placenta and amniotic fluid microbiology. Am J Obstet Gynecol. 1992;166:1382–1388. doi: 10.1016/0002-9378(92)91609-E.
    1. Gibbs RS. Chorioamnionitis and bacterial vaginosis. Am J Obstet Gynecol. 1993;169:460–462. doi: 10.1016/0002-9378(93)90341-F.
    1. Sherman DJ, Tovbin J, Lazarovich T, Avrech O, Reif R, Hoffmann S, Caspi E, Boldur I. Chorioamnionitis caused by gram-negative bacteria as an etiologic factor in preterm birth. Eur J Clin Microbiol Infect Dis. 1997;16:417–423. doi: 10.1007/BF02471905.
    1. Yoon 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. doi: 10.1016/S0029-7844(98)00122-7.
    1. Yoon 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. doi: 10.1067/mob.2000.109036.
    1. Andrews WW, Hauth JC, Goldenberg RL. Infection and preterm birth. Am J Perinatol. 2000;17:357–365. doi: 10.1055/s-2000-13448.
    1. Jacobsson 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. doi: 10.1034/j.1600-0412.2003.00047.x.
    1. Novy MJ, Duffy L, Axthelm MK, Sadowsky DW, Witkin SS, Gravett MG, Cassell GH, Waites KB. Ureaplasma parvum or Mycoplasma hominis as sole pathogens cause chorioamnionitis, preterm delivery, and fetal pneumonia in rhesus macaques. Reprod Sci. 2009;16:56–70. doi: 10.1177/1933719108325508.
    1. Benirschke K. Routes and types of infection in the fetus and the newborn. AMA J Dis Child. 1960;99:714–721.
    1. Blanc WA. Pathways of fetal and early neonatal infection. Viral placentitis, bacterial and fungal chorioamnionitis. J Pediatr. 1961;59:473–496. doi: 10.1016/S0022-3476(61)80232-1.
    1. Martius J, Eschenbach DA. The role of bacterial vaginosis as a cause of amniotic fluid infection, chorioamnionitis and prematurity-a review. Arch Gynecol Obstet. 1990;247:1–13. doi: 10.1007/BF02390649.
    1. Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH, Cotch MF, Edelman R, Pastorek JG 2nd, Rao AV, McNellis D, Regan JA, Carey JC, Klebanoff MA. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med. 1995;333:1737–1742. doi: 10.1056/NEJM199512283332604.
    1. Chaim W, Mazor M, Leiberman JR. The relationship between bacterial vaginosis and preterm birth. A review. Arch Gynecol Obstet. 1997;259:51–58. doi: 10.1007/BF02505309.
    1. Hitti J, Hillier SL, Agnew KJ, Krohn MA, Reisner DP, Eschenbach DA. Vaginal indicators of amniotic fluid infection in preterm labor. Obstet Gynecol. 2001;97:211–219. doi: 10.1016/S0029-7844(00)01146-7.
    1. Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8:3–13. doi: 10.1002/mrdd.10008.
    1. Racicot 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. doi: 10.4049/jimmunol.1300661.
    1. Minkoff H, Grunebaum A, Feldman J, Cummings M, McCormack WM. Relationship of vaginal pH and Papanicolaou smear results to vaginal flora and pregnancy outcome. Int J Gynaecol Obstet. 1987;25:17–23. doi: 10.1016/0020-7292(87)90179-2.
    1. Cotch MF, Pastorek JG 2nd, Nugent RP, Hillier SL, Gibbs RS, Martin DH, Eschenbach DA, Edelman R, Carey JC, Regan JA, Krohn MA, Klebanoff MA, Rao AV, Rhoads GG. Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis. 1997;24:353–360. doi: 10.1097/00007435-199707000-00008.
    1. Andrews WW, Klebanoff MA, Thom EA, Hauth JC, Carey JC, Meis PJ, Caritis SN, Leveno KJ, Wapner RJ, Varner MW, Iams JD, Moawad A, Miodovnik M, Sibai B, Dombrowski M, Langer O, O’Sullivan MJ. Midpregnancy genitourinary tract infection with Chlamydia trachomatis: association with subsequent preterm delivery in women with bacterial vaginosis and Trichomonas vaginalis. Am J Obstet Gynecol. 2006;194:493–500. doi: 10.1016/j.ajog.2005.08.054.
    1. Gravett MG, Nelson HP, DeRouen T, Critchlow C, Eschenbach DA, Holmes KK. Independent associations of bacterial vaginosis and Chlamydia trachomatis infection with adverse pregnancy outcome. JAMA. 1986;256:1899–1903. doi: 10.1001/jama.1986.03380140069024.
    1. Romero R, Mazor M, Oyarzun E, Sirtori M, Wu YK, Hobbins JC. Is genital colonization with Mycoplasma hominis or Ureaplasma urealyticum associated with prematurity/low birth weight? Obstet Gynecol. 1989;73:532–536.
    1. Hillier SL, Krohn MA, Nugent RP, Gibbs RS. Characteristics of three vaginal flora patterns assessed by gram stain among pregnant women. Vaginal Infections and Prematurity Study Group. Am J Obstet Gynecol. 1992;166:938–944. doi: 10.1016/0002-9378(92)91368-K.
    1. Holst E, Goffeng AR, Andersch B. Bacterial vaginosis and vaginal microorganisms in idiopathic premature labor and association with pregnancy outcome. J Clin Microbiol. 1994;32:176–186.
    1. Meis PJ, Goldenberg RL, Mercer B, Moawad A, Das A, McNellis D, Johnson F, Iams JD, Thom E, Andrews WW. The preterm prediction study: significance of vaginal infections. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol. 1995;173:1231–1235. doi: 10.1016/0002-9378(95)91360-2.
    1. Krohn MA, Hillier SL, Nugent RP, Cotch MF, Carey JC, Gibbs RS, Eschenbach DA. The genital flora of women with intraamniotic infection. Vaginal Infection and Prematurity Study Group. J Infect Dis. 1995;171:1475–1480. doi: 10.1093/infdis/171.6.1475.
    1. Andrews WW, Goldenberg RL, Hauth JC. Preterm labor: emerging role of genital tract infections. Infect Agents Dis. 1995;4:196–211.
    1. Goldenberg RL, Thom E, Moawad AH, Johnson F, Roberts J, Caritis SN. The preterm prediction study: fetal fibronectin, bacterial vaginosis, and peripartum infection. NICHD Maternal Fetal Medicine Units Network. Obstet Gynecol. 1996;87:656–660.
    1. Goldenberg RL, Klebanoff MA, Nugent R, Krohn MA, Hillier S, Andrews WW. Bacterial colonization of the vagina during pregnancy in four ethnic groups. Vaginal Infections and Prematurity Study Group. Am J Obstet Gynecol. 1996;174:1618–1621. doi: 10.1016/S0002-9378(96)70617-8.
    1. Jacobsson B, Pernevi P, Chidekel L, Jorgen Platz-Christensen J. Bacterial vaginosis in early pregnancy may predispose for preterm birth and postpartum endometritis. Acta Obstet Gynecol Scand. 2002;81:1006–1010. doi: 10.1034/j.1600-0412.2002.811103.x.
    1. Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C, Husslein P. Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol. 2003;189:139–147. doi: 10.1067/mob.2003.339.
    1. Romero 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. doi: 10.1016/j.ajog.2004.01.002.
    1. Klebanoff MA, Hillier SL, Nugent RP, MacPherson CA, Hauth JC, Carey JC, Harper M, Wapner RJ, Trout W, Moawad A, Leveno KJ, Miodovnik M, Sibai BM, Vandorsten JP, Dombrowski MP, O'Sullivan MJ, Varner M, Langer O. Is bacterial vaginosis a stronger risk factor for preterm birth when it is diagnosed earlier in gestation? Am J Obstet Gynecol. 2005;192:470–477. doi: 10.1016/j.ajog.2004.07.017.
    1. Vogel I, Thorsen P, Hogan VK, Schieve LA, Jacobsson B, Ferre CD. The joint effect of vaginal Ureaplasma urealyticum and bacterial vaginosis on adverse pregnancy outcomes. Acta Obstet Gynecol Scand. 2006;85:778–785. doi: 10.1080/00016340500442423.
    1. Donders GG, Van Calsteren K, Bellen G, Reybrouck R, Van den Bosch T, Riphagen I, Van Lierde S. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG. 2009;116:1315–1324. doi: 10.1111/j.1471-0528.2009.02237.x.
    1. Lee SE, Romero R, Kim EC, Yoon BH. A high Nugent score but not a positive culture for genital mycoplasmas is a risk factor for spontaneous preterm birth. J Matern Fetal Neonatal Med. 2009;22:212–217. doi: 10.1080/14767050802616994.
    1. Lamont RF, Taylor-Robinson D. The role of bacterial vaginosis, aerobic vaginitis, abnormal vaginal flora and the risk of preterm birth. BJOG. 2010;117:119–120. author reply 120–121.
    1. Donders GG, Riphagen I, van den Bosch T. Abnormal vaginal flora, cervical length and preterm birth. Ultrasound Obstet Gynecol. 2000;16:496–497. doi: 10.1046/j.1469-0705.2000.00275-3.x.
    1. Donders GG, Van Calsteren C, Bellen G, Reybrouck R, Van den Bosch T, Riphagen I, Van Lierde S. Association between abnormal vaginal flora and cervical length as risk factors for preterm birth. Ultrasound Obstet Gynecol. 2010. doi:10.1002/uog.7568.
    1. Ward DM, Weller R, Bateson MM. 16 s ribosomal-Rna sequences reveal numerous uncultured microorganisms in a natural community. Nature. 1990;345:63–65. doi: 10.1038/345063a0.
    1. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–1638. doi: 10.1126/science.1110591.
    1. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915–1920. doi: 10.1126/science.1104816.
    1. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449:804–810. doi: 10.1038/nature06244.
    1. Petrosino JF, Highlander S, Luna RA, Gibbs RA, Versalovic J. Metagenomic pyrosequencing and microbial identification. Clin Chem. 2009;55:856–866. doi: 10.1373/clinchem.2008.107565.
    1. Nih HMP, Peterson J, Garges S, Giovanni M, McInnes P, Wang L, Schloss JA, Bonazzi V, McEwen JE, Wetterstrand KA, Deal C, Baker CC, Di Francesco V, Howcroft TK, Karp RW, Lunsford RD, Wellington CR, Belachew T, Wright M, Giblin C, David H, Mills M, Salomon R, Mullins C, Akolkar B, Begg L, Davis C, Grandison L, Humble M, Khalsa J. Working Group et al.The NIH Human Microbiome Project. Genome Res. 2009;19:2317–2323.
    1. Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, Wortman JR, Rusch DB, Mitreva M, Sodergren E, Chinwalla AT, Feldgarden M, Gevers D, Haas BJ, Madupu R, Ward DV, Birren BW, Gibbs RA, Methe B, Petrosino JF, Strausberg RL, Sutton GG, White OR, Wilson RK, Durkin S, Giglio MG, Gujja S, Howarth C, Kodira CD, Kyrpides N, Mehta T. et al.A catalog of reference genomes from the human microbiome. Science. 2010;328:994–999.
    1. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P. et al.A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65. doi: 10.1038/nature08821.
    1. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13:260–270.
    1. Relman DA. Microbiology: learning about who we are. Nature. 2012;486:194–195. doi: 10.1038/486194a.
    1. Pavlova SI, Kilic AO, Kilic SS, So JS, Nader-Macias ME, Simoes JA, Tao L. Genetic diversity of vaginal lactobacilli from women in different countries based on 16S rRNA gene sequences. J Appl Microbiol. 2002;92:451–459. doi: 10.1046/j.1365-2672.2002.01547.x.
    1. Verhelst R, Verstraelen H, Claeys G, Verschraegen G, Delanghe J, Van Simaey L, De Ganck C, Temmerman M, Vaneechoutte M. Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae. Gardnerella vaginalis and bacterial vaginosis. BMC Microbiol. 2004;4:16. doi: 10.1186/1471-2180-4-16.
    1. Zhou X, Bent SJ, Schneider MG, Davis CC, Islam MR, Forney LJ. Characterization of vaginal microbial communities in adult healthy women using cultivation-independent methods. Microbiol. 2004;150:2565–2573. doi: 10.1099/mic.0.26905-0.
    1. Verstraelen H, Verhelst R, Claeys G, Temmerman M, Vaneechoutte M. Culture-independent analysis of vaginal microflora: the unrecognized association of Atopobium vaginae with bacterial vaginosis. Am J Obstet Gynecol. 2004;191:1130–1132. doi: 10.1016/j.ajog.2004.04.013.
    1. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med. 2005;353:1899–1911. doi: 10.1056/NEJMoa043802.
    1. Fredricks DN, Marrazzo JM. Molecular methodology in determining vaginal flora in health and disease: its time has come. Curr Infect Dis Rep. 2005;7:463–470. doi: 10.1007/s11908-005-0049-2.
    1. Hill JE, Goh SH, Money DM, Doyle M, Li A, Crosby WL, Links M, Leung A, Chan D, Hemmingsen SM. Characterization of vaginal microflora of healthy, nonpregnant women by chaperonin-60 sequence-based methods. Am J Obstet Gynecol. 2005;193:682–692. doi: 10.1016/j.ajog.2005.02.094.
    1. Devillard E, Burton JP, Reid G. Complexity of vaginal microflora as analyzed by PCR denaturing gradient gel electrophoresis in a patient with recurrent bacterial vaginosis. Infect Dis Obstet Gynecol. 2005;13:25–31. doi: 10.1155/2005/607474.
    1. Tamrakar R, Yamada T, Furuta I, Cho K, Morikawa M, Yamada H, Sakuragi N, Minakami H. Association between Lactobacillus species and bacterial vaginosis-related bacteria, and bacterial vaginosis scores in pregnant Japanese women. BMC Infect Dis. 2007;7:128. doi: 10.1186/1471-2334-7-128.
    1. Oakley BB, Fiedler TL, Marrazzo JM, Fredricks DN. Diversity of human vaginal bacterial communities and associations with clinically defined bacterial vaginosis. Appl Environ Microbiol. 2008;74:4898–4909. doi: 10.1128/AEM.02884-07.
    1. Brotman RM, Ravel J. Ready or not: the molecular diagnosis of bacterial vaginosis. Clin Infect Dis. 2008;47:44–46. doi: 10.1086/588662.
    1. Trama JP, Pascal KE, Zimmerman J, Self MJ, Mordechai E, Adelson ME. Rapid detection of Atopobium vaginae and association with organisms implicated in bacterial vaginosis. Mol Cell Probes. 2008;22:96–102. doi: 10.1016/j.mcp.2007.08.002.
    1. Menard JP, Fenollar F, Henry M, Bretelle F, Raoult D. Molecular quantification of Gardnerella vaginalis and Atopobium vaginae loads to predict bacterial vaginosis. Clin Infect Dis. 2008;47:33–43. doi: 10.1086/588661.
    1. Marrazzo JM, Thomas KK, Fiedler TL, Ringwood K, Fredricks DN. Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann Intern Med. 2008;149:20–28. doi: 10.7326/0003-4819-149-1-200807010-00006.
    1. Yamamoto T, Zhou X, Williams CJ, Hochwalt A, Forney LJ. Bacterial populations in the vaginas of healthy adolescent women. J Pediatr Adolesc Gynecol. 2009;22:11–18. doi: 10.1016/j.jpag.2008.01.073.
    1. Verstraelen H, Verhelst R, Claeys G, De Backer E, Temmerman M, Vaneechoutte M. Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora. BMC Microbiol. 2009;9:116. doi: 10.1186/1471-2180-9-116.
    1. Lamont RF, Sobel JD, Akins RA, Hassan SS, Chaiworapongsa T, Kusanovic JP, Romero R. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG. 2011;118:533–549. doi: 10.1111/j.1471-0528.2010.02840.x.
    1. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4680–4687.
    1. Aagaard K, Riehle K, Ma J, Segata N, Mistretta TA, Coarfa C, Raza S, Rosenbaum S, Van den Veyver I, Milosavljevic A, Gevers D, Huttenhower C, Petrosino J, Versalovic J. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS One. 2012;7:e36466. doi: 10.1371/journal.pone.0036466.
    1. Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW, Nikita L, Galuppi M, Lamont RF, Chaemsaithong P, Miranda J, Chaiworapongsa T, Ravel J. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014;2:4. doi: 10.1186/2049-2618-2-4.
    1. Pacora 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. doi: 10.1080/jmf.11.1.18.25.
    1. Kingdom J. Placental diagnostic criteria and clinical correlation-a workshop report. Placenta. 2005;26(Suppl A):S114–117.
    1. Redline RW. Inflammatory responses in the placenta and umbilical cord. Semin Fetal Neonatal Med. 2006;11:296–301. doi: 10.1016/j.siny.2006.02.011.
    1. Forney LJ, Gajer P, Williams CJ, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Brotman RM, Davis CC, Ault K, Ravel J. Comparison of self-collected and physician-collected vaginal swabs for microbiome analysis. J Clin Microbiol. 2010;48:1741–1748. doi: 10.1128/JCM.01710-09.
    1. Yuan S, Cohen DB, Ravel J, Abdo Z, Forney LJ. Evaluation of methods for the extraction and purification of DNA from the human microbiome. PLoS One. 2012;7:e33865. doi: 10.1371/journal.pone.0033865.
    1. Frank JA, Reich CI, Sharma S, Weisbaum JS, Wilson BA, Olsen GJ. Critical evaluation of two primers commonly used for amplification of bacterial 16S rRNA genes. Appl Environ Microbiol. 2008;74:2461–2470. doi: 10.1128/AEM.02272-07.
    1. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–214. doi: 10.1038/nature11234.
    1. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–336. doi: 10.1038/nmeth.f.303.
    1. Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010;26:2460–2461. doi: 10.1093/bioinformatics/btq461.
    1. Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27:2194–2200. doi: 10.1093/bioinformatics/btr381.
    1. Matsen FA, Kodner RB, Armbrust EV. Pplacer: linear time maximum-likelihood and Bayesian phylogenetic placement of sequences onto a fixed reference tree. BMC Bioinforma. 2010;11:538. doi: 10.1186/1471-2105-11-538.
    1. Lin J. Divergence measures based on the Shannon entropy. IEEE Trans Information Theory. 1991;37:145–151. doi: 10.1109/18.61115.
    1. Gajer P, Brotman RM, Bai G, Sakamoto J, Schutte UM, Zhong X, Koenig SS, Fu L, Ma ZS, Zhou X, Abdo Z, Forney LJ, Ravel J. Temporal dynamics of the human vaginal microbiota. Sci Transl Med. 2012;4:132ra152.
    1. Lambert D. Zero-Inflated Poisson regression, with an application to defects in manufacturing. Technometrics. 1992;34:1–14. doi: 10.2307/1269547.
    1. Littell CA, Milliken GA, Stroup WW, Wolfinger RD, Schabenberger O. In: SAS for Mixed Models. 2. Littell CA, Milliken GA, Stroup WW, Wolfinger RD, Schabenberger O, editor. Cary, NY: SAS Institute Inc; 2006. Nonlinear mixed models; pp. 567–635.
    1. Zero-Inflated Poisson and Zero-Inflated Negative Binomial Models Using the COUNTREG Procedure. Available at: .
    1. Fredricks DN, Fiedler TL, Thomas KK, Oakley BB, Marrazzo JM. Targeted PCR for detection of vaginal bacteria associated with bacterial vaginosis. J Clin Microbiol. 2007;45:3270–3276. doi: 10.1128/JCM.01272-07.
    1. Yoon 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. doi: 10.1067/mob.2001.117680.
    1. Romero R, Lockwood CJ. In: Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice. 6. Creasy RK, Resnik R, Iams J, editor. Philadelphia: Elsevier; 2009. Pathogenesis of spontaneous preterm labor; pp. 521–543.
    1. Hillier SL, Krohn MA, Cassen E, Easterling TR, Rabe LK, Eschenbach DA. The role of bacterial vaginosis and vaginal bacteria in amniotic fluid infection in women in preterm labor with intact fetal membranes. Clin Infect Dis. 1995;20(Suppl 2):S276–278.
    1. DiGiulio 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. doi: 10.1371/journal.pone.0003056.
    1. DiGiulio 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.
    1. Oh 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.
    1. Donders GG, Vereecken A, Bosmans E, Dekeersmaecker A, Salembier G, Spitz B. Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis. BLOG. 2002;109:34–43.
    1. Donders G, Bellen G, Rezeberga D. Aerobic vaginitis in pregnancy. BLOG. 2011;118:1163–1170.
    1. Hay PE, Lamont RF, Taylor-Robinson D, Morgan DJ, Ison C, Pearson J. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ. 1994;308:295–298. doi: 10.1136/bmj.308.6924.295.
    1. Llahi-Camp JM, Rai R, Ison C, Regan L, Taylor-Robinson D. Association of bacterial vaginosis with a history of second trimester miscarriage. Hum Reprod. 1996;11:1575–1578. doi: 10.1093/oxfordjournals.humrep.a019440.
    1. Ralph SG, Rutherford AJ, Wilson JD. Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study. BMJ. 1999;319:220–223. doi: 10.1136/bmj.319.7204.220.
    1. Donders GG, Van Bulck B, Caudron J, Londers L, Vereecken A, Spitz B. Relationship of bacterial vaginosis and mycoplasmas to the risk of spontaneous abortion. Am J Obstet Gynecol. 2000;183:431–437. doi: 10.1067/mob.2000.105738.
    1. Oakeshott P, Hay P, Hay S, Steinke F, Rink E, Kerry S. Association between bacterial vaginosis or chlamydial infection and miscarriage before 16 weeks’ gestation: prospective community based cohort study. BMJ. 2002;325:1334. doi: 10.1136/bmj.325.7376.1334.
    1. Leitich H, Kiss H. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol. 2007;21:375–390. doi: 10.1016/j.bpobgyn.2006.12.005.
    1. Eschenbach DA, Gravett MG, Chen KC, Hoyme UB, Holmes KK. Bacterial vaginosis during pregnancy. An association with prematurity and postpartum complications. Scan J Urol Nephrol Suppl. 1984;86:213–222.
    1. McGregor JA. Prevention of preterm birth: new initiatives based on microbial-host interactions. Obstet Gynecol Surv. 1988;43:1–14. doi: 10.1097/00006254-198843010-00001.
    1. Hauth JC, Macpherson C, Carey JC, Klebanoff MA, Hillier SL, Ernest JM, Leveno KJ, Wapner R, Varner M, Trout W, Moawad A, Sibai B. Early pregnancy threshold vaginal pH and Gram stain scores predictive of subsequent preterm birth in asymptomatic women. Am J Obstet Gynecol. 2003;188:831–835. doi: 10.1067/mob.2003.184.
    1. Newton ER, Piper J, Peairs W. Bacterial vaginosis and intraamniotic infection. Am J Obstet Gynecol. 1997;176:672–677. doi: 10.1016/S0002-9378(97)70568-4.
    1. Jacobsson B, Mattsby-Baltzer I, Hagberg H. Interleukin-6 and interleukin-8 in cervical and amniotic fluid: relationship to microbial invasion of the chorioamniotic membranes. BJOG. 2005;112:719–724. doi: 10.1111/j.1471-0528.2005.00536.x.
    1. Goldenberg RL, Culhane JF, Johnson DC. Maternal infection and adverse fetal and neonatal outcomes. Clin Perinatol. 2005;32:523–559. doi: 10.1016/j.clp.2005.04.006.
    1. Holst 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. doi: 10.1002/uog.3837.
    1. Watts DH, Eschenbach DA, Kenny GE. Early postpartum endometritis: the role of bacteria, genital mycoplasmas, and Chlamydia trachomatis. Obstet Gynecol. 1989;73:52–60.
    1. Watts DH, Krohn MA, Hillier SL, Eschenbach DA. Bacterial vaginosis as a risk factor for post-cesarean endometritis. Obstet Gynecol. 1990;75:52–58.
    1. Newton ER, Prihoda TJ, Gibbs RS. A clinical and microbiologic analysis of risk factors for puerperal endometritis. Obstet Gynecol. 1990;75:402–406.
    1. Clark P, Kurtzer T, Duff P. Role of bacterial vaginosis in peripartum infections. Infect Dis Obstet Gynecol. 1994;2:179–183. doi: 10.1155/S106474499400061X.
    1. Dammann O, Leviton A. Does prepregnancy bacterial vaginosis increase a mother’s risk of having a preterm infant with cerebral palsy? Dev Med Child Neurol. 1997;39:836–840.
    1. Denney JM, Culhane JF. Bacterial vaginosis: a problematic infection from both a perinatal and neonatal perspective. Semin Fetal Neonatal Med. 2009;14:200–203. doi: 10.1016/j.siny.2009.01.008.
    1. Laxmi U, Agrawal S, Raghunandan C, Randhawa VS, Saili A. Association of bacterial vaginosis with adverse fetomaternal outcome in women with spontaneous preterm labor: a prospective cohort study. J Matern Fetal Neonatal Med. 2012;25:64–67.
    1. Carey 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. doi: 10.1056/NEJM200002243420802.
    1. Klebanoff 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. doi: 10.1056/NEJMoa003329.
    1. Kekki 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. doi: 10.1016/S0029-7844(01)01321-7.
    1. Nygren 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. doi: 10.7326/0003-4819-148-3-200802050-00008.
    1. Lamont 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. doi: 10.1016/j.ajog.2011.03.047.
    1. Brocklehurst P, Gordon A, Heatley E, Milan SJ. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. 2013;1 CD000262.
    1. Macones GA, Parry S, Elkousy M, Clothier B, Ural SH, Strauss JF 3rd. A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth. Am J Obstet Gynecol. 2004;190:1504–1508. doi: 10.1016/j.ajog.2004.01.001. discussion 1503A.
    1. Gomez LM, Sammel MD, Appleby DH, Elovitz MA, Baldwin DA, Jeffcoat MK, Macones GA, Parry S. Evidence of a gene-environment interaction that predisposes to spontaneous preterm birth: a role for asymptomatic bacterial vaginosis and DNA variants in genes that control the inflammatory response. Am J Obstet Gynecol. 2010;202:e381–386.
    1. Genc MR, Onderdonk A. Endogenous bacterial flora in pregnant women and the influence of maternal genetic variation. BJOG. 2011;118:154–163. doi: 10.1111/j.1471-0528.2010.02772.x.
    1. Redline RW, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Pathol Dev. 2003;6:435–448. doi: 10.1007/s10024-003-7070-y.
    1. Elovitz MA, Gajer P, Bastek J, Anglim L, Brown A, Ravel J. The cervicovaginal microbiota is different in women destined to have a preterm birth. Am J Obstet Gynecol. 2014;210:S16–S17.
    1. Morgan XC, Huttenhower C. Chapter 12: human microbiome analysis. PLoS Comput Biol. 2012;8:e1002808. doi: 10.1371/journal.pcbi.1002808.
    1. Nelson DB, Hanlon A, Nachamkin I, Haggerty C, Mastrogiannis DS, Liu C, Fredricks DN. Early pregnancy changes in bacterial vaginosis-associated bacteria and preterm delivery. Pediatr Perinat Epidemiol. 2014;28:88–96. doi: 10.1111/ppe.12106.
    1. Wen A, Srinivasan U, Goldberg D, Owen J, Marrs CF, Misra D, Wing DA, Ponnaluri S, Miles-Jay A, Bucholz B, Abbas K, Foxman B. Selected vaginal bacteria and risk of preterm birth: an ecological perspective. J Infect Dis. 2014;209:1087–1094. doi: 10.1093/infdis/jit632.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다