Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora

Abstract

Bacterial vaginosis (BV) is characterized by a shift in vaginal flora, with a decrease in the prevalence of Lactobacillus and an increase in the prevalence and concentration of anaerobic bacteria, Gardnerella vaginalis, and Mycoplasma hominis. BV, which is consistently associated with preterm delivery, 1,2 is also associated with first-and second-trimester miscarriage, 3,4 amniotic fluid infection, 5,6 histologic chorioamnionitis, 7 and postpartum endometritis. 8 The consistent associations between BV and these markers of upper genital tract infection provide strong indirect evidence that abnormal vaginal flora can ascend to cause bacterial upper genital tract infection and preterm birth. However, most pregnant women with BV have normal pregnancy outcomes.The presence and concentrations of microbial hydrolytic enzymes in women with BV vary. Sialidases (or neuraminidases) are glycosylases that are produced in vitro by several BV-associated bacteria. 9 Prolidase (or proline aminopeptidase) is another hydrolytic enzyme produced by BV-associated bacteria, including G vaginalis and Mobiluncus spp. 10 The only characterized immunogenic virulence factor found in BV thus far is the G vaginalis hemolytic toxin (Gvh). 11,12 The production and concentration of immunoglobulin A (IgA) in response to Gvh in women with BV also vary. Low levels of anti-Gvh IgA in women with BV who are not pregnant are correlated with high levels of vaginal sialidase activity 13 and with cleavage of IgA in vaginal fluid. 14 It remains to be established whether different profiles of these biochemical markers correspond to different levels of risk for poor pregnancy outcome. In the present study, we examined the hypothesis that an increased concentration of sialidase and prolidase and a decreased con- Udine, Italy, Seattle, Wash, and Pittsburgh, Pa OBJECTIVE: The purpose of this study was to determine whether the microbial hydrolytic enzymes, sialidase and prolidase, and immunoglobulin A against the Gardnerella vaginalis cytolysin (anti-Gvh IgA) increase the risk for early preterm birth (≤34 weeks of gestation) among women with bacterial vaginosis or intermediate flora. STUDY DESIGN:Two hundred eighteen afebrile women in preterm labor with intact membranes had a vaginal Gram stain performed, and sialidase, prolidase, and anti-Gvh IgA concentrations were determined. RESULTS: Women with bacterial vaginosis or intermediate flora had significantly higher sialidase and prolidase concentrations than women with normal flora. Among women with bacterial vaginosis or intermediate flora, the women with sialidase had a higher rate of early preterm birth (P = .05). Sialidase had a sensitivity of 43% and specificity of 77% for early preterm birth. Prolidase and anti-Gvh IgA did not predict early preterm birth. CONCLUSION: Women in preterm labor with bacterial vaginosis or intermediate flora and detectable sialidase are at increased risk of early preterm birth. (Am J Obstet Gynecol 2002;187:877-81.)

Evaluation of a Point-of-Care Test, BVBlue, and Clinical and Laboratory Criteria for Diagnosis of Bacterial Vaginosis

“…A difficulty encountered in many diagnostic studies of BV is (3,6,13). A potential application for a sialidase-based test, which remains subject to further research, may be to assist clinicians with determining which women with intermediate flora may be at the greatest risk of sequelae.…”

“…Sialidase promotes adhesion of bacteria to epithelia and also has mucinase activity, which may facilitate invasion of the upper genital tract by BV-associated flora (10,17,27). Elevated bacterial sialidase activity has been significantly associated with BV (2) and with preterm birth in women with BV (3,13). The BVBlue test is a newly developed chromogenic point-of-care test for the diagnosis of BV which is based on detection of increased vaginal fluid sialidase activity (Ն7.8 U).…”

Local Interleukin-1beta in Pregnant Women with Bacterial Vaginosis and Adverse Pregnancy Outcomes

“…BV is a microbial/mucosal immunity disorder [1,3,15,26,27,[29][30][31][32][33]. Accumulating evidence suggests that microbes associated with BV modulate the immune response [27,31,[33][34][35][36].…”

“…The availability of biomarkers early in gestation to predict women at elevated risk of adverse pregnancy outcomes is increasingly appreciated as a necessary pre-requisite for future intervention trials to finally reduce the rate of preterm birth (<37 weeks' gestation) [1][2][3][4][5][6]. Preterm birth (PTB) continues to be a major public health problem with approximately 12% of all US pregnancies ending before 37 weeks' gestation [7].…”

Diagnosis of Bacterial Vaginosis among Symptomatic Egyptian Women: Value of Assessing Bacterial Sialidase Activity

“…Sialidases are secreted from anaerobic Gram-negative bacterial rods such as Bacteroides, Gardnerella, and Prevotella species (Howe et al, 1999;Wiggins et al, 2001;Olmsted et al, 2003). Elevated bacterial sialidase activity has been significantly associated with BV (Wiggins et al, 2000;Myziuk et al, 2003;Akhter et al, 2010;Kampan et al, 2011) and with preterm birth in women with BV (Cauci et al, 2002).…”