Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream

Abstract

Objective: The pathogenesis of preterm birth and other adverse pregnancy outcomes linked with reproductive tract infection remains poorly understood. Mucolytic enzymes, including mucinases and sialidases (neuraminidase), are recognized virulence factors among enteropathogens and bacteria that cause periodontal infection. Perturbation of maternal cervicovaginal mucosa membrane host defenses by such enzyme-producing microorganisms may increase the risk of subclinical intrauterine infection during pregnancy and thus increase risks of preterm birth.

Study design: We prospectively evaluated vaginal fluid mucinase and sialidase and selected cervicovaginal bacteria along with pregnancy outcomes in 271 women. Within this study, women with bacterial vaginosis (16 to 27 week' gestation) were treated with 2% clinadmycin vaginal cream or placebo. Enzyme, microbial findings, treatment effects, and pregnancy outcomes were compared among drug- and placebo-treated women and control women without bacterial vaginosis.

Results: Presence of bacterial vaginosis at intake was associated with increased risk of preterm birth (relative risk 3.3, 95% confidence interval 1.2 to 9.1, p = 0.02), premature rupture of membranes (relative risk 3.8, 95% confidence interval 1.6 to 9.0, p = 0.002), and preterm premature rupture of membranes. Mucinase and sialidase activities were more commonly identified, and they occurred in higher concentrations, if present, in women with bacterial vaginosis (mucinase: 44.3% with bacterial vaginosis vs 27.4% without, p = 0.007; sialidase: 45% with bacterial vaginosis vs 12% without p < 0.001). Sialidase activity was associated with bacterial vaginosis-linked organisms (Gardnerella vaginalis, Mobiluncus spp, and Mycoplasma hominis) and Chlamydia trachomatis and yeast species; mucinase activity was associated only with bacterial vaginosis-linked microorganisms. Clindamycin, 2% cream, was effective treatment for bacterial vaginosis and temporarily reduced mucinase and sialidase activities. Topical treatment of bacterial vaginosis did not reduce risks of perinatal morbidity. Women with persistent or recurrent sialidase 8 weeks after treatment were at increased risk of preterm birth (15.6% vs 7.4%) premature rupture of membranes (30% vs 15%), and low birth weight (20% vs 3%, relative risk 6.8, 95% confidence interval 1.6 to 28.1).

Conclusions: Persistence of sialidase-producing vaginal microorganisms in numbers sufficient to increase vaginal fluid sialidase activity may be a risk factor for possibly preventable subclinical intrauterine infection and preterm birth. This study confirms and further informs our understanding of the association of bacterial vaginosis and preterm birth; studies to evaluate whether systemic treatment for bacterial vaginosis can effectively reduce vaginal mucolytic enzymes and risks of prematurity and other morbid outcomes are continuing.