Association between Bacterial Vaginosis and Preterm Delivery of a Low-Birth-Weight Infant
Sharon L. Hillier, Ph.D., Robert P. Nugent, Ph.D., David A. Eschenbach, M.D., Marijane A. Krohn, Ph.D., Ronald S. Gibbs, M.D., David H. Martin, M.D., Mary Frances Cotch, Ph.D., Robert Edelman, M.D., Joseph G. Pastorek, M.D., A. Vijaya Rao, Ph.D., Donald McNellis, M.D., Joan A. Regan, M.D., J. Christopher Carey, M.D., Mark A. Klebanoff, M.D., for The Vaginal Infections and Prematurity Study Group
Background Bacterial vaginosis is believed to be a risk factorfor preterm delivery. We undertook a study of the associationbetween bacterial vaginosis and the preterm delivery of infantswith low birth weight after accounting for other known riskfactors.
Methods In this cohort study, we enrolled 10,397 pregnant womenfrom seven medical centers who had no known medical risk factorsfor preterm delivery. At 23 to 26 weeks' gestation, bacterialvaginosis was determined to be present or absent on the basisof the vaginal pH and the results of Gram's staining. The principaloutcome variable was the delivery at less than 37 weeks' gestationof an infant with a birth weight below 2500 g.
Results Bacterial vaginosis was detected in 16 percent of the10,397 women. The women with bacterial vaginosis were more likelyto be unmarried, to be black, to have low incomes, and to havepreviously delivered low-birth-weight infants. In a multivariateanalysis, the presence of bacterial vaginosis was related topreterm delivery of a low-birth-weight infant (odds ratio, 1.4;95 percent confidence interval, 1.1 to 1.8). Other risk factorsthat were significantly associated with such a delivery in thispopulation were the previous delivery of a low-birth-weightinfant (odds ratio, 6.2; 95 percent confidence interval, 4.6to 8.4), the loss of an earlier pregnancy (odds ratio, 1.7;1.3 to 2.2), primigravidity (odds ratio, 1.6; 1.1 to 1.9), smoking(odds ratio, 1.4; 1.1 to 1.7); and black race (odds ratio, 1.4;1.1 to 1.7). Among women with bacterial vaginosis, the highestrisk of preterm delivery of a low-birth-weight infant was foundamong those with both vaginal bacteroides and Mycoplasmahominis(odds ratio, 2.1; 95 percent confidence interval, 1.5 to 3.0).
Conclusions Bacterial vaginosis was associated with the pretermdelivery of low-birth-weight infants independently of otherrecognized risk factors.
Source Information
From the University of Washington, Seattle (S.L.H., D.A.E., M.A. Krohn); the National Institute of Child Health and Human Development, Bethesda, Md. (R.P.N., D.M., M.A. Klebanoff); the University of Texas, San Antonio (R.G.); Louisiana State University, New Orleans (D.H.M., J.G.P.); the National Institute of Allergy and Infectious Diseases, Bethesda, Md. (M.F.C., R.E.); the Research Triangle Institute, Research Triangle Park, N.C. (A.V.R.); Columbia University, New York (J.A.R.); and the University of Oklahoma, Oklahoma City (J.C.C.).
Address reprint requests to Dr. Hillier at University of Pittsburgh/Magee–Women's Hospital, Department of Obstetrics, Gynecology, and Reproductive Sciences, 300 Halket St., Pittsburgh, PA 15213.
Arbyn, M, Kyrgiou, M, Simoens, C, Raifu, A O, Koliopoulos, G, Martin-Hirsch, P, Prendiville, W, Paraskevaidis, E
(2008). Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ
337: a1284-a1284
[Abstract][Full Text]
Xu, J., Holzman, C. B., Arvidson, C. G., Chung, H., Goepfert, A. R.
(2008). Midpregnancy Vaginal Fluid Defensins, Bacterial Vaginosis, and Risk of Preterm Delivery. Obstet Gynecol
112: 524-531
[Abstract][Full Text]
Oakley, B. B., Fiedler, T. L., Marrazzo, J. M., Fredricks, D. N.
(2008). Diversity of Human Vaginal Bacterial Communities and Associations with Clinically Defined Bacterial Vaginosis. Appl. Environ. Microbiol.
74: 4898-4909
[Abstract][Full Text]
Brotman, R. M., Klebanoff, M. A., Nansel, T. R., Andrews, W. W., Schwebke, J. R., Zhang, J., Yu, K. F., Zenilman, J. M., Scharfstein, D. O.
(2008). A Longitudinal Study of Vaginal Douching and Bacterial Vaginosis--A Marginal Structural Modeling Analysis. Am J Epidemiol
168: 188-196
[Abstract][Full Text]
Nygren, P., Fu, R., Freeman, M., Bougatsos, C., Klebanoff, M., Guise, J.-M.
(2008). 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
148: 220-233
[Abstract][Full Text]
Cherpes, T L, Marrazzo, J M, Cosentino, L A, Meyn, L A, Murray, P J, Hillier, S L
(2008). Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis. Sex. Transm. Infect.
84: 57-61
[Abstract][Full Text]
Marrazzo, J. M
(2007). Elusive aetiology of bacterial vaginosis. Do lesbians have a clue?. Sex. Transm. Infect.
83: 424-425
[Full Text]
Smith, L. K., Draper, E. S., Manktelow, B. N., Field, D. J.
(2007). Deprivation and Infection Among Spontaneous Very Preterm Births. Obstet Gynecol
110: 325-329
[Abstract][Full Text]
Robertson, S. A., Care, A. S., Skinner, R. J.
(2007). Interleukin 10 Regulates Inflammatory Cytokine Synthesis to Protect Against Lipopolysaccharide-Induced Abortion and Fetal Growth Restriction in Mice. Biol. Reprod.
76: 738-748
[Abstract][Full Text]
Cauci, S., Di Santolo, M., Casabellata, G., Ryckman, K., Williams, S. M., Guaschino, S.
(2007). Association of interleukin-1{beta} and interleukin-1 receptor antagonist polymorphisms with bacterial vaginosis in non-pregnant Italian women. Mol Hum Reprod
13: 243-250
[Abstract][Full Text]
Allsworth, J. E., Peipert, J. F.
(2007). Prevalence of Bacterial Vaginosis: 2001 2004 National Health and Nutrition Examination Survey Data. Obstet Gynecol
109: 114-120
[Abstract][Full Text]
Keane, F, Ison, C A, Noble, H, Estcourt, C
(2006). Bacterial vaginosis. Sex. Transm. Infect.
82: iv16-iv18
[Full Text]
Tann, C J, Mpairwe, H, Morison, L, Nassimu, K, Hughes, P, Omara, M, Mabey, D, Muwanga, M, Grosskurth, H, Elliott, A M
(2006). Lack of effectiveness of syndromic management in targeting vaginal infections in pregnancy in Entebbe, Uganda.. Sex. Transm. Infect.
82: 285-289
[Abstract][Full Text]
Roberton, A. M., Wiggins, R., Horner, P. J., Greenwood, R., Crowley, T., Fernandes, A., Berry, M., Corfield, A. P.
(2005). A Novel Bacterial Mucinase, Glycosulfatase, Is Associated with Bacterial Vaginosis. J. Clin. Microbiol.
43: 5504-5508
[Abstract][Full Text]
Thompson, L. A., Goodman, D. C., Chang, C.-H., Stukel, T. A.
(2005). Regional Variation in Rates of Low Birth Weight. Pediatrics
116: 1114-1121
[Abstract][Full Text]
Waites, K. B., Katz, B., Schelonka, R. L.
(2005). Mycoplasmas and Ureaplasmas as Neonatal Pathogens. Clin. Microbiol. Rev.
18: 757-789
[Abstract][Full Text]
Austin, M. N., Beigi, R. H., Meyn, L. A., Hillier, S. L.
(2005). Microbiologic Response to Treatment of Bacterial Vaginosis with Topical Clindamycin or Metronidazole. J. Clin. Microbiol.
43: 4492-4497
[Abstract][Full Text]
Mullick, S, Watson-Jones, D, Beksinska, M, Mabey, D
(2005). Sexually transmitted infections in pregnancy: prevalence, impact on pregnancy outcomes, and approach to treatment in developing countries. Sex. Transm. Infect.
81: 294-302
[Abstract][Full Text]
Bradshaw, C. S., Morton, A. N., Garland, S. M., Morris, M. B., Moss, L. M., Fairley, C. K.
(2005). Higher-Risk Behavioral Practices Associated With Bacterial Vaginosis Compared With Vaginal Candidiasis. Obstet Gynecol
106: 105-114
[Abstract][Full Text]
Okun, N., Gronau, K. A., Hannah, M. E.
(2005). Antibiotics for Bacterial Vaginosis or Trichomonas vaginalis in Pregnancy: A Systematic Review. Obstet Gynecol
105: 857-868
[Abstract][Full Text]
Bradshaw, C. S., Morton, A. N., Garland, S. M., Horvath, L. B., Kuzevska, I., Fairley, C. K.
(2005). Evaluation of a Point-of-Care Test, BVBlue, and Clinical and Laboratory Criteria for Diagnosis of Bacterial Vaginosis. J. Clin. Microbiol.
43: 1304-1308
[Abstract][Full Text]
Bhutta, Z. A., Darmstadt, G. L., Hasan, B. S., Haws, R. A.
(2005). Community-Based Interventions for Improving Perinatal and Neonatal Health Outcomes in Developing Countries: A Review of the Evidence. Pediatrics
115: 519-617
[Abstract][Full Text]
Ramsey, P. S., Lyon, M. D., Goepfert, A. R., Cliver, S., Schwebke, J., Andrews, W. W., Goldenberg, R. L., Hauth, J. C.
(2005). Use of Vaginal Polymorphonuclear to Epithelial Cell Ratios for the Prediction of Preterm Birth. Obstet Gynecol
105: 139-144
[Abstract][Full Text]
Ferris, M. J., Masztal, A., Martin, D. H.
(2004). Use of Species-Directed 16S rRNA Gene PCR Primers for Detection of Atopobium vaginae in Patients with Bacterial Vaginosis. J. Clin. Microbiol.
42: 5892-5894
[Abstract][Full Text]
Chaudry, A. N., Travers, P. J., Yuenger, J., Colletta, L., Evans, P., Zenilman, J. M., Tummon, A.
(2004). Analysis of Vaginal Acetic Acid in Patients Undergoing Treatment for Bacterial Vaginosis. J. Clin. Microbiol.
42: 5170-5175
[Abstract][Full Text]
Ugwumadu, A., Reid, F., Hay, P., Manyonda, I.
(2004). Natural History of Bacterial Vaginosis and Intermediate Flora in Pregnancy and Effect of Oral Clindamycin. Obstet Gynecol
104: 114-119
[Abstract][Full Text]
Yudin, M. H., Landers, D. V., Meyn, L., Hillier, S. L.
(2003). Clinical and Cervical Cytokine Response to Treatment With Oral or Vaginal Metronidazole for Bacterial Vaginosis During Pregnancy: A Randomized Trial. Obstet Gynecol
102: 527-534
[Abstract][Full Text]
Ahern, J, Pickett, K E, Selvin, S, Abrams, B
(2003). Preterm birth among African American and white women: a multilevel analysis of socioeconomic characteristics and cigarette smoking. J. Epidemiol. Community Health
57: 606-611
[Abstract][Full Text]
Reid, G, Bruce, A W
(2003). Urogenital infections in women: can probiotics help?. Postgrad. Med. J.
79: 428-432
[Abstract][Full Text]
Yoshida, T., Maeda, S.-I., Deguchi, T., Miyazawa, T., Ishiko, H.
(2003). Rapid Detection of Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum Organisms in Genitourinary Samples by PCR-Microtiter Plate Hybridization Assay. J. Clin. Microbiol.
41: 1850-1855
[Abstract][Full Text]
Myziuk, L., Romanowski, B., Johnson, S. C.
(2003). BVBlue Test for Diagnosis of Bacterial Vaginosis. J. Clin. Microbiol.
41: 1925-1928
[Abstract][Full Text]
Onderdonk, A. B., Lee, M.-L., Lieberman, E., Delaney, M. L., Tuomala, R. E.
(2003). Quantitative Microbiologic Models for Preterm Delivery. J. Clin. Microbiol.
41: 1073-1079
[Abstract][Full Text]
Lamont, R. F., Duncan, S. L. B., Mandal, D., Bassett, P.
(2003). Intravaginal Clindamycin to Reduce Preterm Birth in Women With Abnormal Genital Tract Flora. Obstet Gynecol
101: 516-522
[Abstract][Full Text]
Cauci, S., Thorsen, P., Schendel, D. E., Bremmelgaard, A., Quadrifoglio, F., Guaschino, S.
(2003). Determination of Immunoglobulin A against Gardnerella vaginalis Hemolysin, Sialidase, and Prolidase Activities in Vaginal Fluid: Implications for Adverse Pregnancy Outcomes. J. Clin. Microbiol.
41: 435-438
[Abstract][Full Text]
Cauci, S., Guaschino, S., de Aloysio, D., Driussi, S., De Santo, D., Penacchioni, P., Quadrifoglio, F.
(2003). Interrelationships of interleukin-8 with interleukin-1{beta} and neutrophils in vaginal fluid of healthy and bacterial vaginosis positive women. Mol Hum Reprod
9: 53-58
[Abstract][Full Text]
Nelson, D. B., Macones, G.
(2002). Bacterial Vaginosis in Pregnancy: Current Findings and Future Directions. Epidemiol Rev
24: 102-108
[Full Text]
Martino, J. L., Vermund, S. H.
(2002). Vaginal Douching: Evidence for Risks or Benefits to Women's Health. Epidemiol Rev
24: 109-124
[Full Text]
Workowski, K. A., Levine, W. C., Wasserheit, J. N.
(2002). U.S. Centers for Disease Control and Prevention Guidelines for the Treatment of Sexually Transmitted Diseases: An Opportunity To Unify Clinical and Public Health Practice. ANN INTERN MED
137: 255-262
[Abstract][Full Text]
Ruiz, R. J., Fullerton, J., Brown, C. E. L., Dudley, D. J.
(2002). Predicting Risk of Preterm Birth: The Roles of Stress, Clinical Risk Factors, and Corticotropin-Releasing Hormone. Biol Res Nurs
4: 54-64
[Abstract]
Cauci, S., Driussi, S., De Santo, D., Penacchioni, P., Iannicelli, T., Lanzafame, P., De Seta, F., Quadrifoglio, F., de Aloysio, D., Guaschino, S.
(2002). Prevalence of Bacterial Vaginosis and Vaginal Flora Changes in Peri- and Postmenopausal Women. J. Clin. Microbiol.
40: 2147-2152
[Abstract][Full Text]
Yoshida, T., Maeda, S.-I., Deguchi, T., Ishiko, H.
(2002). Phylogeny-Based Rapid Identification of Mycoplasmas and Ureaplasmas from Urethritis Patients. J. Clin. Microbiol.
40: 105-110
[Abstract][Full Text]
Holzman, C., Leventhal, J. M., Qiu, H., Jones, N. M., Wang, J.
(2001). Factors Linked to Bacterial Vaginosis in Nonpregnant Women. Am. J. Public Health
91: 1664-1670
[Abstract][Full Text]
Delaney, M. L., Onderdonk, A. B.
(2001). Nugent Score Related to Vaginal Culture in Pregnant Women. Obstet Gynecol
98: 79-84
[Abstract][Full Text]
KEKKI, M., KURKI, T., PELKONEN, J., KURKINEN-RATY, M., CACCIATORE, B., PAAVONEN, J.
(2001). Vaginal Clindamycin in Preventing Preterm Birth and Peripartal Infections in Asymptomatic Women With Bacterial Vaginosis: A Randomized, Controlled Trial. Obstet Gynecol
97: 643-648
[Abstract][Full Text]
Shahmanesh, M.
(2001). Why common things are common: the tale of non-gonococcal urethritis. Sex. Transm. Infect.
77: 139-140
[Full Text]
Schulpen, T W J, van Steenbergen, J E, van Driel, H F
(2001). Influences of ethnicity on perinatal and child mortality in the Netherlands. Arch. Dis. Child.
84: 222-226
[Abstract][Full Text]
Morris, M C, Rogers, P A, Kinghorn, G R
(2001). Is bacterial vaginosis a sexually transmitted infection?. Sex. Transm. Infect.
77: 63-68
[Abstract][Full Text]
Kilic, A. O., Pavlova, S. I., Alpay, S., Kilic, S. S., Tao, L.
(2001). Comparative Study of Vaginal Lactobacillus Phages Isolated from Women in the United States and Turkey: Prevalence, Morphology, Host Range, and DNA Homology. CVI
8: 31-39
[Abstract][Full Text]
Li, X., Kolltveit, K. M., Tronstad, L., Olsen, I.
(2000). Systemic Diseases Caused by Oral Infection. Clin. Microbiol. Rev.
13: 547-558
[Abstract][Full Text]
MASTROBATTISTA, J. M., BISHOP, K. D., NEWTON, E. R.
(2000). Wet Smear Compared With Gram Stain Diagnosis of Bacterial Vaginosis in Asymptomatic Pregnant Women. Obstet Gynecol
96: 504-506
[Abstract][Full Text]
Marrazzo, J. M
(2000). Sexually transmitted infections in women who have sex with women: who cares?. Sex. Transm. Infect.
76: 330-332
[Full Text]
Jarosik, G. P., Land, C. B.
(2000). Identification of a Human Lactoferrin-Binding Protein in Gardnerella vaginalis. Infect. Immun.
68: 3443-3447
[Abstract][Full Text]
Goldenberg, R. L., Hauth, J. C., Andrews, W. W.
(2000). Intrauterine Infection and Preterm Delivery. NEJM
342: 1500-1507
[Full Text]
KURKI, T., HIILESMAA, V., RAITASALO, R., MATTILA, H., YLIKORKALA, O.
(2000). Depression and Anxiety in Early Pregnancy and Risk for Preeclampsia. Obstet Gynecol
95: 487-490
[Abstract][Full Text]
Carey, J. C., Klebanoff, M. A., Hauth, J. C., Hillier, S. L., Thom, E. A., Ernest, J.M., Heine, R. P., Nugent, R. P., Fischer, M. L., Leveno, K. J., Wapner, R., Varner, M., Trout, W., Moawad, A., Sibai, B. M., Miodovnik, M., Dombrowski, M., O'Sullivan, M. J., VanDorsten, J. P., Langer, O., Roberts, J., The National Institute of Child Health Human Devel,
(2000). Metronidazole to Prevent Preterm Delivery in Pregnant Women with Asymptomatic Bacterial Vaginosis. NEJM
342: 534-540
[Abstract][Full Text]
Sanders, M. E.
(2000). Considerations for Use of Probiotic Bacteria to Modulate Human Health. J. Nutr.
130: 384-384
[Abstract][Full Text]
Mackler, A. M., Ducsay, C. A., Veldhuis, J. D., Yellon, S. M.
(1999). Maturation of Spontaneous and Agonist-Induced Uterine Contractions in the Peripartum Mouse Uterus. Biol. Reprod.
61: 873-878
[Abstract][Full Text]
Mackler, A.M., Iezza, G., Akin, M.R., McMillan, P., Yellon, S.M.
(1999). Macrophage Trafficking in the Uterus and Cervix Precedes Parturition in the Mouse. Biol. Reprod.
61: 879-883
[Abstract][Full Text]
Norwitz, E. R., Robinson, J. N., Challis, J. R.G.
(1999). The Control of Labor. NEJM
341: 660-666
[Full Text]
Merchant, J. S., Oh, M. K., Klerman, L. V.
(1999). Douching: A Problem for Adolescent Girls and Young Women. Arch Pediatr Adolesc Med
153: 834-837
[Abstract][Full Text]
Ralph, S G, Rutherford, A J, Wilson, J D
(1999). Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study. BMJ
319: 220-223
[Abstract][Full Text]
Nowicki, B., Singhal, J., Fang, L., Nowicki, S., Yallampalli, C.
(1999). Inverse Relationship between Severity of Experimental Pyelonephritis and Nitric Oxide Production in C3H/HeJ Mice. Infect. Immun.
67: 2421-2427
[Abstract][Full Text]
Pal, S., Peterson, E. M., de la Maza, L. M.
(1999). A Murine Model for the Study of Chlamydia trachomatis Genital Infections during Pregnancy. Infect. Immun.
67: 2607-2610
[Abstract][Full Text]
FRENCH, J. I., MCGREGOR, J. A., DRAPER, D., PARKER, R., MCFEE, J.
(1999). Gestational Bleeding, Bacterial Vaginosis, and Common Reproductive Tract Infections: Risk for Preterm Birth and Benefit of Treatment. Obstet Gynecol
93: 715-724
[Abstract][Full Text]
CRANE, J. M. G., ANTHONY ARMSON, B., DODDS, L., FEINBERG, R. F., KENNEDY, W., KIRKLAND, S. A.
(1999). Risk Scoring, Fetal Fibronectin, and Bacterial Vaginosis to Predict Preterm Delivery. Obstet Gynecol
93: 517-522
[Abstract][Full Text]
Brocklehurst, P.
(1999). Infection and preterm delivery. BMJ
318: 548-549
[Full Text]
PASTORE, L. M., ROYCE, R. A., JACKSON, T. P., THORP, J. M. Jr, SAVITZ, D. A., KREADEN, U. S.
(1999). Association Between Bacterial Vaginosis and Fetal Fibronectin at 24-29 Weeks' Gestation. Obstet Gynecol
93: 117-123
[Abstract][Full Text]
Kogan, M. D., Martin, J. A., Ventura, S. J., Alexander, G. R., Kotelchuck, M., Frigoletto, F. D., Rosenberg, K. D., Rooks, J. P., Misra, D. P., Guyer, B., Kogan, M. D., Martin, J. A., Ventura, S. J., Alexander, G. R., Kotelchuck, M., Frigoletto, F. D.
(1998). Benefits and Limitations of Prenatal Care. JAMA
280: 2071-2073
[Full Text]
Jarosik, G. P., Land, C. B., Duhon, P., Chandler, R. Jr., Mercer, T.
(1998). Acquisition of Iron by Gardnerella vaginalis. Infect. Immun.
66: 5041-5047
[Abstract][Full Text]
Goldenberg, R. L., Rouse, D. J.
(1998). Prevention of Premature Birth. NEJM
339: 313-320
[Full Text]
Schuchat, A.
(1998). Epidemiology of Group B Streptococcal Disease in the United States: Shifting Paradigms. Clin. Microbiol. Rev.
11: 497-513
[Abstract][Full Text]
Muli, F., Struthers, J. K.
(1998). Use of a Continuous-Culture Biofilm System To Study the Antimicrobial Susceptibilities of Gardnerella vaginalis and Lactobacillus acidophilus. Antimicrob. Agents Chemother.
42: 1428-1432
[Abstract][Full Text]
Darveau, R. P., Belton, C. M., Reife, R. A., Lamont, R. J.
(1998). Local Chemokine Paralysis, a Novel Pathogenic Mechanism for Porphyromonas gingivalis. Infect. Immun.
66: 1660-1665
[Abstract][Full Text]
Murdoch, D. A.
(1998). Gram-Positive Anaerobic Cocci. Clin. Microbiol. Rev.
11: 81-120
[Abstract][Full Text]
McGregor, J. A., French, J. I., Bloom, B. S., Lee, D. W., Hauth, J. C., Hillier, S. L.
(1996). Bacterial Vaginosis and Preterm Birth. NEJM
334: 1337-1339
[Full Text]
(1996). BACTERIAL VAGINOSIS AND PRETERM DELIVERY. JWatch General
1996: 1-1
[Full Text]
Hack, M., Merkatz, I. R.
(1995). Preterm Delivery and Low Birth Weight -- A Dire Legacy. NEJM
333: 1772-1774
[Full Text]
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