Relationship between Vaginal Bacterial Infections and Pregnancy Outcomes: A Systematic Review and Meta Analysis

Hojjat Rokni, Amjad Ahmadi, Yousef Moradi, Bijan Nouri, Daem Roshani

Abstract


Background: Bacterial infections are among the most serious infections worldwide. They can cause miscarriage, premature birth, stillbirth, and ectopic pregnancy in pregnant women. The aim of this study was to investigate the relationship between bacterial infections and pregnancy outcomes through a systematic review and meta‑analysis.

Materials and Methods: PubMed, Scopus, Web of Science, and Embase databases were searched from January 2000 to December 2018 using appropriate keywords to identify related articles. The final related studies were selected and evaluated using the Newcastle‑Ottawa Scale (NOS).

Results: Results of this meta‑analysis based on combining case‑control studies showed that the presence of bacterial infections could lead increase in the odds of all pregnancy outcomes like premature infant birth (odd ratio [OR]: 1.50; 95% Confidence Interval [CI], 1.39–1.61), preterm delivery (OR: 1.54; 95% CI, 1.39–1.70), abortion (OR: 1.16; 95% CI, 1.04–1.29), stillbirth (OR, 1.29; 95% CI, 1.12–1.49), and ectopic pregnancy (OR: 1.12; 95% CI, 1.05–‑1.19). The results showed that the Risk Ratio (RR) of preterm delivery in pregnant women with vaginal infections was 1.57 (95% CI, 1.46–1.67), whereas the RR of abortion was 2.02 (95% CI, 1.72–2.38).

Conclusions: Based on the results of this meta‑analysis, the presence of bacterial infections in pregnant women can lead increase in the risk of pregnancy outcomes especially, preterm delivery, abortion, stillbirth, and ectopic pregnancy. Therefore, it is necessary for obstetricians and gynecologists to pay attention to the diagnosis of these infections in women before pregnancy and during pregnancy in order to prevent the consequences of these infections.



Keywords


Abortion, bacterial infections, ectopic pregnancy, premature births, stillbirths

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References


Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta analyses: The PRISMA statement. PLoS Med 2009;6:e1000097.

Roßmann J, Gummer T, Kaczmirek L. Working with user agent strings in Stata: The PARSEUAS command. Journal of Statistical Software 2020;92:1 16.

DerSimonian R, Laird N. Meta analysis in clinical trials. Control Clin Trials 1986;7:177 88.

Pustejovsky JE, Rodgers MA. Testing for funnel plot asymmetry of standardized mean differences. Res Synth Methods 2019;10:57 71.

Jacobsson B, Pernevi P, Chidekel L, Jörgen Platz Christensen J. Bacterial vaginosis in early pregnancy may predispose for preterm birth and postpartum endometritis. Acta Obstet Gynecol Scand 2002;81:1006 10.

Afolabi BB, Moses OE, Oduyebo OO. Bacterial vaginosis and pregnancy outcome in Lagos, Nigeria. Open Forum Infect Dis 2016;3:ofw030. doi: 10.1093/ofid/ofw030.

Aaltone R, Jalava J, Laurikainen E, Karkkainen U, Alanen A. Cervical ureaplasma urealyticum colonization: Comparison of PCR and culture for its detection and association with preterm birth. Scand J Infect Dis 2002;34:35 40.

Averbach SH, Hacker MR, Yiu T, Modest AM, Dimitrakoff J, Ricciotti HA. Mycoplasma genitalium and preterm delivery at an urban community health center. Int J Gynecol Obstet 2013;123:54 7.

Azargoon A, Darvishzadeh S. Association of bacterial vaginosis, Trichomonas vaginalis, and vaginal acidity with outcome of pregnancy. Arch Iran Med 2006;9:213 7.

Bakken IJ, Skjeldestad FE, Lydersen S, Nordbo SA. Births and ectopic pregnancies in a large cohort of women tested for Chlamydia trachomatis. Sex Transm Dis 2007;34:739 43.

Balu RB, Savitz DA, Ananth CV, Hartmann KE, Miller WC, Thorp JM, et al. Bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth. Obstet Gynecol 2003;101:862 8.

Blas MM, Canchihuaman FA, Alva IE, Hawes SE. Pregnancy outcomes in women infected with Chlamydia trachomatis: A population based cohort study in Washington State. Sex Transm Infect 2007;83:314 8.

Bretelle F, Rozenberg P, Pascal A, Favre R, Bohec C, Loundou A, et al. High Atopobium vaginae and Gardnerella vaginalis vaginal loads are associated with preterm birth. Clin Infect Dis 2015;60:860 7.

Daskalakis G, Papapanagiotou A, Mesogitis S, Papantoniou N, Mavromatis K, Antsaklis A. Bacterial vaginosis and group B streptococcal colonization and preterm delivery in a low risk population. Fetal Diagn Ther 2006;21:172 6.

De Borborema Alfaia APB, De Lima Freitas NS, Filho SA, Borborema Santos CM. Chlamydia trachomatis infection in a sample of northern Brazilian pregnant women: Prevalence and prenatal importance. Braz J Infect Dis 2013;17:545 50.

Dingens AS, Fairfortune TS, Reed S, Mitchell C. Bacterial vaginosis and adverse outcomes among full term infants: A cohort study. BMC Pregnancy Childbirth 2016;16:278.

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 7.

Fahmy MM, Abd El Salam SMS, Emarah MA, ElSobky AA. Value of transvaginal cervical ultrasonographic assessment and bacterial vaginosis in prediction of preterm Birth. Life Sci J 2015;12:35 40.

Harper LM, Parry S, Stamilio DM, Odibo AO, Cahill AG, Strauss JF, et al. The interaction effect of bacterial vaginosis and periodontal disease on the risk of preterm delivery. Am J Perinatol 2012;29:347 51.

Hollegaard S, Vogel I, Thorsen P, Jensen IP, Mordhorst CH, Jeune B. Chlamydia trachomatis C complex serovars are a risk factor for preterm birth. In Vivo 2007;21:107 12.

Lata I, Pradeep Y, Sujata S, Jain A. Estimation of the incidence of bacterial vaginosis and other vaginal infections and its consequences on maternal/fetal outcome in pregnant women attending an antenatal clinic in a tertiary care hospital in North India. Indian J Community Med 2010;35:285 9.

McPheeters ML, Miller WC, Hartmann KE, Savitz DA, Kaufman JS, Garrett JM, et al. The epidemiology of threatened preterm labor: A prospective cohort study. Am J Obstet Gynecol 2005;192:1325 30.

Menard JP, Mazouni C, Salem Cherif I, Fenollar F, Raoult D, Boubli L, et al. High vaginal concentrations of atopobium vaginae and gardnerella vaginalis in women undergoing preterm labor. Obstet Gynecol 2010;115:134 40.

Nelson DB, Bellamy S, Clothier BA, Macones GA, Nachamkin I, Ruffin A, et al. Characteristics and pregnancy outcomes of pregnant women asymptomatic for bacterial vaginosis. Matern Child Health J 2008;12:216 22.

Nelson DB, Hanlon A, Hassan S, Britto J, Geifman Holtzman O, Haggerty C, et al. Preterm labor and bacterial vaginosis associated bacteria among urban women. J Perinat Med 2009;37:130 4.

Nelson DB, Hanlon A, Nachamkin I, Haggerty C, Mastrogiannis DS, Liu CZ, et al. Early pregnancy changes in bacterial vaginosis associated bacteria and preterm delivery. Paediatr Perinat Epidemiol 2014;28:88 96.

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. Br Med J 2002;325:1334 6.

Odendaal HJ, Schoeman J, Grové D, de Jager M, Theron GB, Orth H, et al. The association between Chlamydia trachomatis genital infection and spontaneous preterm labour. S Afr J Obs Gyn 2006;12:146 9.

Rittenschober Böhm J, Waldhoer T, Schulz SM, Stihsen B, Pimpel B, Goeral K, et al. First trimester vaginal ureaplasma biovar colonization and preterm birth: Results of a prospective multicenter study. Neonatology 2017;113:1 6.

Rours G, Duijts L, Moll HA, Arends LR, de Groot R, Jaddoe VW, et al. Chlamydia trachomatis infection during pregnancy associated with preterm delivery: A population based prospective cohort study. Eur J Epidemiol 2011;26:493 502.

Tellapragada C, Eshwara VK, Bhat P, Acharya S, Kamath A, Bhat S, et al. Risk factors for preterm birth and low birth weight among pregnant Indian women: A hospital based prospective study. J Prev Med Public Health 2016;49:165 75.

Thorsen P, Vogel I, Olsen J, Jeune B, Westergaard JG, Jacobsson B, et al. Bacterial vaginosis in early pregnancy is associated with low birth weight and small for gestational age, but not with spontaneous preterm birth: A population based study on Danish women. J Matern Fetal Neonatal Med 2006;19:1 7.

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 85.

Watson Jones D, Changalucha J, Gumodoka B, Weiss H, Rusizoka M, Ndeki L, et al. Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy. J Infect Dis 2002;186:940 7.

Bylykbashi E, Kosturi E, Demaliaj E, Rrugia A, Bylykbashi I. The impact of bacterial vaginosis, Trichomonas vaginalis and vaginal acidity on pregnancy outcome. G Ital Ostet Ginecol 2013;35:160 1.

Carlini L, Somigliana E, Rossi G, Veglia F, Busacca M, Vignali M. Risk factors for spontaneous preterm birth: A northern Italian multicenter case control study. Gynecol Obstet Invest 2002;53:174 80.

Discacciati MG, Simoes JA, Silva MG, Marconi C, Brolazo E, Costa ML, et al. Microbiological characteristics and inflammatory cytokines associated with preterm labor. Arch Gynecol Obstet 2011;283:501 8.

Isik G, Demirezen S, Donmez HG, Beksac MS. Bacterial vaginosis in association with spontaneous abortion and recurrent pregnancy losses. J Cytol 2016;33:135 40.

Lim KH, Brooks H, McDougal R, Burton J, Devenish C, De Silva T. Is there a correlation between bacterial vaginosis and preterm labour in women in the Otago region of New Zealand? Aust New Zealand J Obstet Gynaecol 2010;50:226 9.

Marakoglu I, Gursoy UK, Marakoglu K, Cakmak H, Ataoglu T. Periodontitis as a risk factor for preterm low birth weight. Yonsei Med J 2008;49:200 3.

Agger WA, Siddiqui D, Lovrich SD, Callister SM, Borgert AJ, Merkitch KW, et al. Epidemiologic factors and urogenital infections associated with preterm birth in a Midwestern U.S. population. Obstet Gynecol 2014;124:969 77.

Agholor K, Omo Aghoja L, Okonofua F. Association of anti Chlamydia antibodies with ectopic pregnancy in Benin city, Nigeria: A case control study. Afr Health Sci 2013;13:430 40.

Ahmadi A, Khodabandehloo M, Ramazanzadeh R, Farhadifar F, Roshani D, Ghaderi E, et al. The relationship between chlamydia trachomatis genital infection and spontaneous abortion. J Reprod Infertil 2016;17:110 6.

Andrews WW, Goldenberg RL, Mercer B, Iams J, Meis P, Moawad A, et al. The preterm prediction study: Association of second trimester genitourinary chlamydia infection with subsequent spontaneous preterm birth. Am J Obstet Gynecol 2000;183:662 8.

Bakken IJ, Skjeldestad FE, Nordbo SA. Chlamydia trachomatis infections increase the risk for ectopic pregnancy: A population based, nested case control study. Sex Transm Dis 2007;34:166 9.

Baud D, Goy G, Jaton K, Osterheld MC, Blumer S, Borel N, et al. Role of Chlamydia trachomatis in miscarriage. Emerg Infect Dis 2011;17:1630 5.

Baud D, Goy G, Vasilevsky S, Osterheld MC, Roth Kleiner M, Croxatto A, et al. Roles of bovine Waddlia chondrophila and Chlamydia trachomatis in human preterm birth. New Microbes New Infect 2015;3:41 5.

Benjamin MA, Yaakub R, Paul M, Md Yusof J, Osman O. Role of chlamydial infection in ectopic pregnancy. Brunei Int Med J 2013;9:97 101.

Karaer A, Mert I, Cavkaytar S, Batioglu S. Serological investigation of the role of selected sexually transmitted infections in the aetiology of ectopic pregnancy. Eur J Contracept Reprod Health Care 2013;18:68 74.

Karinen D, Pouta A, Bloigu A, Koskela P, Paidanius M, Leinonen M, et al. Serum C reactive protein and Chlamlydia trachomatis antibodies in preterm delivery. Obstet Gynecol 2005;106:73 80.

Mpiima DP, Salongo GW, Lugobe H, Ssemujju A, Mulisya OM, Masinda A, et al. Association between Prior Chlamydia trachomatis Infection and Ectopic Pregnancy at a Tertiary Care Hospital in South Western Uganda. Obstet Gynecol Int 2018;2018:4827353. doi: 10.1155/2018/4827353.

Abele Horn M, Scholz M, Wolff C, Kolben M. High density vaginal Ureaplasma urealyticum colonization as a risk factor for chorioamnionitis and preterm delivery. Acta Obstet Gynecol Scand 2000;79:973 8.

Hitti J, Garcia P, Totten P, Paul K, Astete S, Holmes KK. Correlates of cervical Mycoplasma genitalium and risk of preterm birth among Peruvian women. Sex Transm Dis 2010;37:81 5.

Jurstrand M, Jensen JS, Magnuson A, Karnwendo F, Fredlund H. A serological study of the role of Mycoplasma genitalium in pelvic inflammatory disease and ectopic pregnancy. Sex Transm Infect 2007;83:319 23.

Ahmadi A, Khodabandehloo M, Ramazanzadeh R, Farhadifar F, Nikkhoo B, Soofizade N, et al. Association between Ureaplasma urealyticum endocervical infection and spontaneous abortion in Sanandaj, Iran. Iran J Microbiol 2014;6:392 7.

Harada K, Tanaka H, Komori S, Tsuji Y, Nagata K, Tsutsui H, et al. Vaginal infection with Ureaplasma urealyticum accounts for preterm delivery via induction of inflammatory responses. Microbiol Immunol 2008;52:297 304.

Kafetzis DA, Skevaki CL, Skouteri V, Gavrili S, Peppa K, Kostalos C, et al. 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 2004;39:1113 22.

Farhadifar F, Khodabandehloo M, Ramazanzadeh R, Rouhi S, Ahmadi A, Ghaderi E, et al. Survey on association between Mycoplasma hominis endocervical infection and spontaneous abortion using polymerase chain reaction. Int J Reprod Biomed 2016;14:181 6.

Arnesen L, Martinez G, Mainero L, Serruya S, Duran P. Gestational syphilis and stillbirth in Latin America and the Caribbean. Int J Gynecol Obstet 2015;128:241 5.

Dou L, Wang X, Wang F, Wang Q, Qiao Y, Su M, et al. Epidemic profile of maternal syphilis in China in 2013. Biomed Res Int 2016;2016:9194805. doi: 10.1155/2016/9194805.

Geelhoed D, Stokx J, Mariano X, Lázaro CM, Roelens K. Risk factors for stillbirths in Tete, Mozambique. Int J Gynecol Obstet 2015;130:148 52.

Ahmadi A, Farhadifar F, Rezaii M, Zandvakili F, Seyedoshohadaei F, Zarei M, et al. Group B streptococci and trichomonas vaginalis infections in pregnant women and those with spontaneous abortion at Sanandaj, Iran. Iran J Microbiol 2018;10:166 70.

Buchmayer S, Sparén P, Cnattingius S. Signs of infection in Pap smears and risk of adverse pregnancy outcome. Paediatr Perinat Epidemiol 2003;17:340 6.

Kamal AM, Ahmed AK, Mowafy NMES, Shawki HE, Sanad AS, Hassan EE. Incidence of antenatal trichomoniasis and evaluation of its role as a cause of preterm birth in pregnant women referring to Minia University hospital, Egypt. Iran J Parasitol 2018;13:58 66.

Eleje GU, Adinma JI, Ugwuanyi DC, Ikechebelu JI, Okafor CI, Ezeama CO, et al. Genital tract microbial isolate in women with preterm pre labour rupture of membranes in resource constrained community setting. J Obstet Gynaecol 2015;35:465 8.

Heumann CL, Quilter LAS, Eastment MC, Heffron R, Hawes SE. Adverse birth outcomes and maternal Neisseria gonorrhoeae infection: A population based cohort study in Washington State. Sex Transm Dis 2017;44:266 71.

Nejad VM, Shafaie S. The association of bacterial vaginosis and preterm labor. J Pak Med Assoc 2008;58:104 6.

Pereira TB, Thomaz EB, Nascimento FR, Santos AP, Batista RL, Bettiol H, et al. Regulatory cytokine expression and preterm birth: Case control study nested in a cohort. PLoS One 2016;11:e0158380.

Subtil D, Denoit V, Gouëff FL, Husson MO, Trivier D, Puech F. The role of bacterial vaginosis in preterm labor and preterm birth: A case control study. Eur J Obstet Gynecol Reprod Biol 2002;101:41 6.

Svare JA, Schmidt H, Hansen BB, Lose G. Bacterial vaginosis in a cohort of Danish pregnant women: prevalence and relationship with preterm delivery, low birthweight and perinatal infections. BJOG 2007;114:510-1.

Ashshi AM, Batwa SA, Kutbi SY, Malibary FA, Batwa M, Refaat B. Prevalence of 7 sexually transmitted organisms by multiplex real time PCR in Fallopian tube specimens collected from Saudi women with and without ectopic pregnancy. BMC Infect Dis 2015;15:569.

Burton AE, Thomas S. Sexually transmitted infections and preterm birth among Indigenous women of the Northern Territory, Australia: A case control study. Aust New Zealand J Obstet Gynaecol 2019;59:147 53.

Donders GG, Van Calsteren K, Bellen G, Reybrouck R, Van Den Bosch T, Riphagen I, et al. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG Int J Obstet Gynaecol 2009;116:1315 24.

Edwards RK, Ferguson RJ, Reyes L, Brown M, Theriaque DW, Duff P. Assessing the relationship between preterm delivery and various microorganisms recovered from the lower genital tract. J Matern Fetal Neonatal Med 2006;19:357 63.

Kataoka S, Yamada T, Chou K, Nishida R, Morikawa M, Minami M, et al. Association between preterm birth and vaginal colonization by mycoplasmas in early pregnancy. J Clin Microbiol 2006;44:51 5.

Kilpatrick SJ, Patil R, Connell J, Nichols J, Studee L. Risk factors for previable premature rupture of membranes or advanced cervical dilation: A case control study. Am J Obstet Gynecol 2006;194:1168 74.

Nakubulwa S, Kaye DK, Bwanga F, Tumwesigye NM, Mirembe FM. Genital infections and risk of premature rupture of membranes in Mulago Hospital, Uganda: A case control study womens health. BMC Res Notes 2015;8:573.

Nyári T, Woodward M, Mészáaros G, Karsai J, Kovács L. Chlamydia trachomatis infection and the risk of perinatal mortality in Hungary. J Perinat Med 2001;29:55 9.

Pientong C, Ekalaksananan T, Wonglikitpanya N, Swadpanich U, Kongyingyoes B, Kleebkaow P. Chlamydia trachomatis infections and the risk of ectopic pregnancy in Khon Kaen women. J Obstet Gynaecol Res 2009;35:775 81.

Rantsi T, Joki Korpela P, Wikstrom E, Ohman H, Bloigu A, Lehtinen M, et al. Population based study of prediagnostic antibodies to chlamydia trachomatis in relation to adverse pregnancy outcome. Sex Transm Dis 2016;43:382 7.

Zhu Q, Li C, Zhao WH, Yuan JJ, Yan MX, Qin GJ, et al. Risk factors and clinical features of ovarian pregnancy: A case control study. BMJ Open 2014;4:e006447.

Povlsen K, Thorsen P, Lind I. Relationship of Ureaplasma urealyticum biovars to the presence or absence of bacterial vaginosis in pregnant women and to the time of delivery. Eur J Clin Microbiol Infect Dis 2001;20:65 7.

Schwab FD, Zettler EK, Moh A, Schötzau A, Gross U, Günthert AR. Predictive factors for preterm delivery under rural conditions in post tsunami Banda Aceh. J Perinat Med 2016;44:511 5.

Silveira MF, Ghanem KG, Erbelding EJ, Burke AE, Johnson HL, Singh RH, et al. Chlamydia trachomatis infection during pregnancy and the risk of preterm birth: A case control study. Int J STD AIDS 2009;20:465 9.

Ramazanzadeh R, Khodabandehloo M, Farhadifar F, Rouhi S, Ahmadi A, Menbari S, et al. A case control study on the relationship between mycoplasma genitalium infection in women with normal pregnancy and spontaneous abortion using polymerase chain reaction. Osong Public Health Res Perspect 2016;7:334 8.

Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW, Bieda J, et al. The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Microbiome 2014;2:18.

Ahmadi A, Ramazanzadeh R, Sayehmiri K, Sayehmiri F, Amirmozafari N. Association of Chlamydia trachomatis infections with preterm delivery; a systematic review and meta-analysis. BMC pregnancy and childbirth. 2018;18:1-7.

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 Gyneco. 2003;189:139-47.

He W, Jin Y, Zhu H, Zheng Y, Qian J. Effect of Chlamydia trachomatis on adverse pregnancy outcomes: a meta-analysis. Arch Gynecol Obstet. 2020;302:553-67.


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