Cost-effectiveness of screening and treatment for bacterial vaginosis in early pregnancy among women at low risk for preterm birth

BACKGROUND: Bacterial vaginosis (BV) is an important risk factor for preterm birth. BV is detected in 10-30% of pregnant women and is often asymptomatic. Treatment of BV during pregnancy seems to reduce the risk of preterm delivery among high-risk women. We performed a cost-effectiveness analysis of screening and treatment for BV in early pregnancy among asymptomatic women at low risk for preterm delivery. METHODS: A decision tree was built with two arms. For the screening (and treatment) arm the probabilities were derived from our earlier randomized trial on screening and treatment for BV, consisting of BV-positive women treated with intravaginal clindamycin cream or placebo and also of BV-negative pregnant women. The probabilities of outcomes among these women were collected from antenatal clinic records and hospital records, and for the no-screening arm mainly from the Finnish Perinatal Statistics. The outcomes considered were preterm delivery, mode of delivery, peripartum infections and postpartum complications. The unit costs associated with these outcomes were mainly based on disease-related groups (DRGs). No-screening was compared with two screening programs (one with clindamycin, the other with metronidazole treatment) and subjected to sensitivity analyses. RESULTS: There was no significant difference between screening and no-screening strategies in the costs and in the rate of preterm deliveries but the screening strategy produced significantly fewer peripartum infections and postpartum complications. Sensitivity analyses suggested that the screening strategy may become cost-saving if the rate of preterm deliveries exceeds 3%. CONCLUSION: Screening and treatment for BV in early pregnancy may not reduce costs compared to no-screening in a population at low risk for preterm birth but would produce, at the same cost, more health benefits in terms of fewer peripartum infections and postpartum complications. However, it may be cost-saving if the rate of preterm deliveries is higher than 3%.     

Bacterial vaginosis and preterm birth

Although it has been clear for more than 2 decades that bacterial vaginosis increases the risk for preterm birth in some women, it is not yet fully understood why this association exists or how best to modify the risk. Incomplete understanding of this polymicrobial condition and difficulties in classification contribute to the challenge. The relationship between altered vaginal microflora and preterm birth is likely mediated by host immune responses. Because treatment of bacterial vaginosis during pregnancy does not improve preterm birth rates, and may in fact increase them, screening and treatment of asymptomatic pregnant women is discouraged. Symptomatic women should be treated for symptom relief. This article reviews the pathophysiology of bacterial vaginosis and controversy surrounding management during pregnancy. Agents currently recommended for treatment of this condition are reviewed.     

The relationship between bacterial vaginosis and preterm birth. A review

Bacterial vaginosis is currently the most prevalent form of vaginal infection of reproductive age women. The etiology of bacterial vaginosis has not yet been defined. However, clear criteria for diagnosis and treatment have been established in the absence as well as in presence of pregnancy. Recent data show an association between bacterial vaginosis and preterm labor and delivery. This review outlines the role of bacterial vaginosis in preterm birth and other pregnancy complications.     

The relationship between periodontal disease, bacterial vaginosis, and preterm birth

Spontaneous preterm labor leading to preterm birth is a major cause of perinatal mortality and morbidity worldwide. The etiology of spontaneous preterm labor is multifactoral but there is overwhelming evidence to implicate infection in up to 40% of cases. Historically, this infective link has focused on the associations between abnormal genital tract flora in pregnancy (diagnosed by the presence of bacterial vaginosis) and preterm birth. Recently, another condition related to abnormal flora (periodontal disease) has been linked with preterm birth. There are microbiological similarities between the oral cavity and the female genital tract giving rise to a possible common pathophysiology. This review records the interrelationship between periodontal disease, bacterial vaginosis, and preterm birth. We postulate on the mechanism linking the three conditions, particularly through microbiology and gene-environmental interactions. Periodontal disease and bacterial vaginosis may be risk factors in their own rights or may be interrelated. We speculate on whether periodontitisis a marker for an immune hyperresponse to abnormal flora which in the oral cavity results in periodontitis and in the case of bacterial vaginosis might result in preterm birth. We also postulate on the risk of preterm birth by periodontitis alone, bacterial vaginosis alone, or both.     

Sexual intercourse association with asymptomatic bacterial vaginosis and Trichomonas vaginalis treatment in relationship to preterm birth

OBJECTIVE: The purpose of this study was to determine whether sexual intercourse was associated with the treatment efficacy or the incidence of preterm birth in two large randomized trials in which metronidazole treatment of bacterial vaginosis or Trichomonas vaginalis did not reduce preterm birth. STUDY DESIGN: Secondary analysis of two multicenter, double-blind, placebo-controlled trials in which women with asymptomatic bacterial vaginosis on Gram stain or asymptomatic T vaginalis on culture were randomized at 16 to 23 weeks of gestation to metronidazole or placebo. In both studies, women took 2 g of metronidazole or placebo in the presence of a nurse (first dose) and were given a second dose to take 48 hours later. This regimen was repeated (third and fourth doses) at 24 to 29 weeks. At the time of the third dose, bacterial vaginosis and T vaginalis specimens were collected again. Patients who were randomly selected to receive metronidazole were analyzed for bacterial vaginosis and T vaginalis at 24 to 29 weeks and for preterm birth of <37 weeks of gestation, according to intercourse between first and second doses and between the second and third doses. Continuous variables were compared with the use of the Wilcoxon rank-sum test; categoric variables were compared with the use of the chi(2 ) test, Fisher exact test, or the Mantel-Haenzel test of trend. RESULTS: Sexual intercourse between the first and second doses or between the second and third doses did not influence the incidence of bacterial vaginosis (18% vs 24%; relative risk, 0.7; 95% CI, 0.5-1.1; and 23% vs 20%; relative risk, 1.2; 95% CI, 0.9-1.6, respectively) or T vaginalis (4% vs 8%; relative risk, 0.5; 95% CI, 0.1-3.6; and 5% vs 10%; relative risk, 0.5; 95% CI, 0.2-1.1; respectively) at 24 to 29 weeks of gestation compared with no intercourse. In the T vaginalis trial, sexual intercourse between the first and second doses or between the second and third doses did not influence the incidence of preterm birth (13% vs 17%; relative risk, 0.8; 95% CI, 0.3-2.1; and 16% vs 17%; relative risk, 1.0; 95% CI, 0.6-1.6; respectively) compared with no intercourse. In the bacterial vaginosis trial, although sexual intercourse between the first and second doses did not influence the incidence of preterm birth (11% vs 12%; relative risk, 0.9; 95 % CI, 0.6-1.5), sexual intercourse between the second and third doses was associated with a reduction in the incidence of preterm birth (10% vs 16%; relative risk, 0.6; 95% CI, 0.4-0.9) compared with no intercourse. CONCLUSION: Sexual intercourse was associated with neither the efficacy of metronidazole treatment of bacterial vaginosis or T vaginalis nor with the incidence of preterm birth. In the bacterial vaginosis study, intercourse between the second and third doses had a negative association with preterm birth.     

Prevention of preterm birth is possible by vaginal pH screening, early diagnosis of bacterial vaginosis or abnormal vaginal flora and treatment

Abnormal vaginal flora as well as bacterial vaginosis have a significant relative risk for miscarriage or preterm birth of 1.4-6.9. In the initial Erfurt trial, 0.3% of the neonates with gestational age <32+0 weeks were seen in an intervention group vs. 3.3% (p < 0.01) in the control group; in the larger Thuringia campaign, the figures were 0.94 vs. 1.36% (p < 0.01). The rate of newborns <1,000 g was reduced to 0.38%, the lowest incidence ever seen in any of the German states. This should count even more, as there was no success in reducing the rate of low-birth-weight children in the decades preceding these prospective studies. However, after discontinuation of the campaign in 2000, the preterm birth rates mounted in 2005 in our hospital and the state to the same rate as prior to the programme.     

The role of bacterial vaginosis in preterm labor and preterm birth: a case-control study.

OBJECTIVE: To study the association between preterm labor and bacterial vaginosis; in women with preterm labor, to determine whether vaginosis modifies the risk of preterm delivery. STUDY DESIGN: Case-control study. We used Amsel's clinical criteria to test 102 patients hospitalized for preterm labor and 102 control patients for bacterial vaginosis. RESULTS: Patients with preterm labor were diagnosed with bacterial vaginosis significantly more often (13.8%, 95% confidence interval (CI) (7.7-22.0) than control patients (0.0%, 95% CI (0.0-3.6)) (P<0.001). Among the former, the time elapsed to delivery was identical regardless of the patient's bacterial vaginosis status (elapsed time: 35.9 versus 37.1 days, rate of spontaneous preterm birth 42.9 versus 43.2%, not significant). CONCLUSION: Bacterial vaginosis is associated with preterm labor. Nonetheless, it does not appear to predict preterm birth among these patients.     

Bacterial vaginosis in early pregnancy may predispose for preterm birth and postpartum endometritis

BACKGROUND: Bacterial vaginosis (BV) has been reported to be associated with spontaneous preterm delivery and infectious morbidity after birth in non-Swedish populations. Our intention was to investigate the situation in a Swedish population. METHODS: In this cohort study, 924 patients were enrolled consecutively. A Papanicolaou (Pap) smear, which included a posterior fornix sample, was obtained at the first visit (median: 12 weeks and 1 day) at the two antenatal care units in central G?teborg 1990-91. Clue cells in the Pap smear were considered to be consistent with BV. The principal outcome variables were spontaneous preterm birth (< 37 weeks) and postpartum endometritis. A relative risk (RR) was calculated with a 95% confidence interval. RESULTS: The prevalence of BV was 15.6%. An association was seen between BV in early pregnancy and postpartum endometritis [RR 3.26 (1.38-7.71)]. A non-significant association was found between BV and spontaneous preterm birth [RR 2.10 (0.90-4.94)]. A multiple logistic regression analysis was performed adjusting for primi-/multiparity and antibiotics during pregnancy and the odds ratio was 2.16 (0.87-3.64). CONCLUSIONS: The prevalence of BV was 15.6% in this Swedish pregnant population. The risk for postpartum endometritis was tripled among women with BV in early pregnancy. The risk for spontaneous preterm birth among women with BV was doubled but non-significant, although the samples were obtained early in pregnancy.     

Fetal fibronectin and bacterial vaginosis are associated with preterm birth in women who are symptomatic for preterm labor

OBJECTIVE: The purpose of this study was to codify the relationship between bacterial vaginosis/fetal fibronectin and preterm labor/birth. STUDY DESIGN: In this prospective study, 185 women who were symptomatic for preterm labor were assessed for bacterial vaginosis and fetal fibronectin. RESULTS: These women comprised 4 groups: group A (n=23 women; +bacterial vaginosis/+fetal fibronectin); group B (n=31 women; -bacterial vaginosis/+fetal fibronectin); group C (n=47 women; +bacterial vaginosis/-fetal fibronectin); and group D (n=84 women; -bacterial vaginosis/-fetal fibronectin). The time interval from gestational age at testing until delivery was significantly shorter for groups A and B versus groups C and D (P < or =.05 and P <.001, respectively). Similarly, delivery at <32 weeks of gestation was increased in group B (26%) compared with groups A (9%), C (2%), and D (5%; P <.009; odds ratio, 165.90; 95% CI, 30.02, 916.08). CONCLUSION: Women who are symptomatic for preterm labor should be considered for fetal fibronectin and bacterial vaginosis testing.     

Aetiology of preterm labour: bacterial vaginosis

Bacterial vaginosis (BV) is a common condition characterised by a polymicrobial disorder, with an overgrowth of several anaerobic or facultative bacteria and with a reduction or absence of lactobacillus colonisation. The prevalence of BV ranges from 4 to 64%, depending on the racial, geographic and clinical characteristics of the study population. In asymptomatic women, the prevalence varies from 12 to 25%, and similar percentages are observed in pregnant women. Although BV is associated with several adverse outcomes, such as upper genital tract infections, pelvic inflammatory disease, endometritis, preterm birth and low birthweight, many basic questions regarding the pathogenesis of BV remain unanswered. Mucosal immune system activation may represent a critical determinant of adverse consequences associated with BV. An unequal risk for BV acquisition and\or recurrence could derive from different mucosal immune host abilities and\or capability of invading microbes to produce factors that inactivate the local immune response. BV is associated with a two-fold increased risk of preterm birth, with the greatest risk when BV is present before 16 weeks of gestation (odds ratio = 7.55). This may indicate a critical period during early gestation when BV-related organisms can gain access to the upper genital tract and set the stage for spontaneous preterm labour later in gestation. The results of treatment trials for pregnant women with BV have been heterogeneous, with anywhere from an 80% reduction to a two-fold increase in preterm birth among women who received treatment. For this reason, in current clinical practice significant controversy surrounds determining not only who and when to screen but also who and how to treat. Recent evidence shows that individual genetic backgrounds can affect chemokine production. This is an interesting area for future research and could lead to trials of treatment only for women genetically predisposed to preterm birth.     

Periodontal disease and bacterial vaginosis as genetic and environmental markers for the risk of spontaneous preterm labor and preterm birth

Objective.?The aim of this study was to review the evidence associating periodontal disease, and bacterial vaginosis with preterm birth, and the link with gene polymorphism, as well as the preventions and interventions which might reduce the risk of spontaneous preterm labor and preterm births in women with periodontal disease and/or bacterial vaginosis.

Background.?Preterm birth accounts for 70% of perinatal mortality, nearly 50% of long term neurological morbidity, and a significant impact on health care costs. There is evidence that spontaneous preterm labor and preterm birth are associated with intrauterine infection due to abnormal genital and/or oral colonization. Periodontal disease and bacterial vaginosis share microbiological similarities, and both conditions are associated with spontaneous preterm labor and preterm birth. In addition, periodontal disease and bacterial vaginosis have been linked through gene polymorphism.

Methods.?A review of the literature using widely accepted scientific search engines in English language.

Results.?Studies evaluating antibiotic administration to eradicate periodontal disease and/or bacterial vaginosis responsible organisms, and minimize the risk of preterm births have yielded conflicting results. With respect to bacterial vaginosis, the timing and the choice of antibiotic administration might partly explain the conflicting results. The use of scaling and/or root planning for women with periodontal disease appears to reduce the risk of preterm birth, but routine administration of antibiotics has not demonstrated any impact on preterm birth.

Conclusion.?Prospective studies evaluating the association of gene polymorphism with preterm birth, and the contribution of periodontal disease and bacterial vaginosis are needed.     

The effect of treating bacterial vaginosis on preterm labor

OBJECTIVE: Multiple studies suggest that bacterial vaginosis (BV) causes preterm labor; yet its routine treatment remains controversial. In order to help to elucidate this controversy, we performed a thorough review of studies with levels of evidence ranging from I to II-II. METHODS: We searched for all of the studies from the years 1994 to 2001 via Medline's database, including MD Consult and Ovid Mednet. RESULTS: Several trials discovered a decrease in the incidence of preterm labor when BV was treated, but most of those trials were performed on women with a history of preterm labor. However, the majority of trials reviewed advise against treatment of a general low-risk obstetric population, as there was no significant decrease in preterm labor. CONCLUSIONS: Therefore, based on the above studies and the current guidelines of the Centers for Disease Control and Prevention (CDC), treating pregnant women in high-risk populations who are diagnosed with BV provides the clinician with an opportunity to possibly prevent preterm labor in this population. In nulliparous women without a history of preterm birth, treatment is recommended if other risk factors are present (e.g. gonorrhea or chlamydia). However, in the general low-risk populations, routine screening is not indicated.     

Relationships of vaginal Lactobacillus species, cervical Chlamydia trachomatis, and bacterial vaginosis to preterm birth

The frequency of genital infection was compared among women in premature labor who delivered preterm (before 37 weeks), women in preterm labor who delivered at term, and control women who delivered at term. Both groups of women in premature labor were younger and had more previous preterm births than did control women. Women in premature labor who delivered preterm were more likely to experience rupture of membranes, intrapartum fever, and postpartum fever than were control women. The presence of bacterial vaginosis (odds ratio 2.3) and Chlamydia trachomatis (odds ratio 3.9) was positively associated, and Lactobacillus sp (odds ratio 0.2) was negatively associated, with birth before 37 weeks, using multivariable analysis to control for confounding variables.     

Effect of oral N-acetyl cysteine on recurrent preterm labor following treatment for bacterial vaginosis

OBJECTIVE: To evaluate the effect of N-acetyl cysteine (NAC) on gestational age at delivery in women with previous preterm labor and bacterial vaginosis. METHODS: A randomized, double-blind, placebo-controlled trial with 280 women between 16 and 18 weeks of pregnancy who had 1 previous preterm birth and had just been successfully treated for bacterial vaginosis with metronidazole for 1 week. The women were randomized to receive 0.6 g of NAC per day plus 17-hydroxyprogesterone caproate (17-OHPC) or placebo plus 17-OHPC until 36 completed weeks of pregnancy or active labor. A vaginal swab was taken during labor. RESULTS: Reaching 36 weeks of pregnancy was more frequent (P<0.05) and gestational age at delivery was significantly higher in the NAC than in the placebo group (37.4 weeks+/-0.4 weeks vs 34.1 weeks+/-1.2 weeks, P<0.05). The discontinuation rate was 11.4% in the NAC group. CONCLUSIONS: Oral NAC was found to reduce the recurrence of preterm birth in patients with bacterial vaginosis.