McGregor J A, French J I, Jones W, Milligan K, McKinney P J, Patterson E, Parker R
Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver 80262.
Am J Obstet Gynecol. 1994 Apr;170(4):1048-59; discussion 1059-60. doi: 10.1016/s0002-9378(94)70098-2.
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.
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.
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).
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.
早产及其他与生殖道感染相关的不良妊娠结局的发病机制仍未完全明确。包括黏蛋白酶和唾液酸酶(神经氨酸酶)在内的黏液溶解酶是肠道病原体及引起牙周感染的细菌中公认的毒力因子。此类产酶微生物对母体宫颈阴道黏膜宿主防御功能的干扰可能会增加孕期亚临床宫内感染的风险,进而增加早产风险。
我们前瞻性评估了271名女性的阴道液黏蛋白酶和唾液酸酶以及选定的宫颈阴道细菌,并观察了妊娠结局。在本研究中,患有细菌性阴道病(妊娠16至27周)的女性接受2%克林霉素阴道乳膏或安慰剂治疗。比较了接受药物和安慰剂治疗的女性以及无细菌性阴道病的对照女性的酶、微生物检测结果、治疗效果和妊娠结局。
入组时患有细菌性阴道病与早产风险增加相关(相对风险3.3,95%置信区间1.2至9.1,p = 0.02)、胎膜早破(相对风险3.8,95%置信区间1.6至9.0,p = 0.002)以及早产胎膜早破。黏蛋白酶和唾液酸酶活性在患有细菌性阴道病的女性中更常见,且如果存在,其浓度更高(黏蛋白酶:细菌性阴道病患者中为44.3%,无细菌性阴道病患者中为27.4%,p = 0.007;唾液酸酶:细菌性阴道病患者中为45%,无细菌性阴道病患者中为12%,p < 0.001)。唾液酸酶活性与细菌性阴道病相关微生物(阴道加德纳菌、动弯杆菌属和人型支原体)、沙眼衣原体和酵母菌种属相关;黏蛋白酶活性仅与细菌性阴道病相关微生物相关。2%的克林霉素乳膏是治疗细菌性阴道病的有效药物,可暂时降低黏蛋白酶和唾液酸酶活性。局部治疗细菌性阴道病并未降低围产期发病风险。治疗8周后唾液酸酶持续或复发的女性早产风险增加(15.6%对7.4%)、胎膜早破风险增加(30%对15%)以及低出生体重风险增加(20%对3%,相对风险6.8,95%置信区间1.6至28.1)。
产生唾液酸酶的阴道微生物数量持续存在,足以增加阴道液唾液酸酶活性,这可能是可预防的亚临床宫内感染和早产的一个风险因素。本研究证实并进一步加深了我们对细菌性阴道病与早产关联的理解;评估细菌性阴道病的全身治疗是否能有效降低阴道黏液溶解酶以及早产和其他不良结局风险的研究仍在继续。