An Update Review for the U.S. Preventive Services Task Force
Peggy Nygren, MA; Rongwei Fu, PhD; Michele Freeman, MPH; Christina Bougatsos, BS; Mark Klebanoff, MD, MPH; and
Jeanne-Marie Guise, MD, MPH
The authors of this article are responsible for its contents,
including any clinical or treatment recommendations. No statement in
this article should be construed as an official position of the Agency for
Healthcare Research and Quality or the U.S. Department of Health and
Human Services.
This article was first published in the Annals of Internal Medicine. Select for copyright and source information.
Contents
Abstract
Introduction
Methods
Results
Discussion
References
Notes
Appendix: Outcomes Table Methodology
Abstract
Background: Bacterial vaginosis is the most common lower genital
tract syndrome among women of reproductive age. There has been
continued debate about the value of screening and treating asymptomatic
pregnant women for bacterial vaginosis.
Purpose: To examine new evidence on the benefits and harms of
screening and treating bacterial vaginosis in asymptomatic pregnant
women.
Data Sources: English-language studies on Ovid MEDLINE® (2000
to September 2007) and Cochrane Library databases (through September
2007), reference lists, and expert suggestions.
Study Selection: Screening, treatment, or adverse effect studies
with pregnancy outcome data in women who are asymptomatic for
bacterial vaginosis.
Data Extraction: Study and patient characteristics, treatment variables,
adverse pregnancy outcomes, and internal validity quality
criteria from the U.S. Preventive Services Task Force (USPSTF) and
Jadad scale were abstracted.
Data Synthesis: 7 new randomized, controlled treatment trials and
2001 report data were combined in a series of meta-analyses to
estimate the pooled effect of treatment on preterm delivery (<37,
<34, and <32 weeks); low birthweight; and preterm, premature
rupture of membranes.
Limitations: No screening studies that compared a screened population
with a nonscreened population were found. Significant heterogeneity
was found among the high-risk treatment trials (P <0.001). It is not clear from the detailed description of the studies
which factors explain the differences in preterm delivery rates and
potentially the association of treatment effect; however, both raise
concern for the unintended potential for harm.
Conclusion: No benefit was found in treating women with low- or
average-risk pregnancies for asymptomatic bacterial vaginosis.
More research is needed to better understand these groups and the
conditions under which treatment can be harmful or helpful, and to
explore the relevance of bacterial vaginosis to other adverse pregnancy
outcomes, such as delivery before 34 weeks.
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Introduction
Bacterial vaginosis is the most common lower genital
tract syndrome in women of reproductive age.1 It
involves an imbalance in the vaginal bacterial ecosystem,
such that hydrogen peroxide-producing lactobacilli are diminished
and Gardnerella vaginalis, anaerobes, and mycoplasmata
are abundant. Symptoms can include vaginal discharge,
pruritus, or malodor, although approximately half
of women with bacterial vaginosis are asymptomatic.2-4
Once the condition is diagnosed, the microflora imbalance
can be altered with a short course of antibiotic therapy;
however, recurrence is common. The natural history of
bacterial vaginosis in pregnant women has shown that up
to 50% of cases of bacterial vaginosis resolve spontaneously
during pregnancy.5,6 Although several antibiotic treatment
regimens have been shown to effectively eradicate
bacterial vaginosis in pregnant women,7 the treatments
recommended in pregnancy by the Centers for Disease
Control and Prevention are oral metronidazole (250 mg 3
times daily for 7 days) or oral clindamycin (300 mg twice
daily for 7 days).8,9
Researchers have documented the associations between
bacterial vaginosis and adverse pregnancy outcomes, focusing
on preterm birth and, more recently, the timing of
treatment.4,10-20 This epidemiologic evidence has
been used as a rationale for screening asymptomatic pregnant
women. The prevalence of bacterial vaginosis in pregnant
women seen in community settings is not well studied.
In several large, prospective, longitudinal studies, the
rate of bacterial vaginosis has ranged from 9% to 23%.11-13,21-23 Nearly one quarter of white women in an
NHANES (National Health and Nutrition Examination
Survey) probability sample had Gram stains consistent
with bacterial vaginosis.24 Bacterial vaginosis in pregnancy
may be more common among minority women,
those of low socioeconomic status, and those who have
previously delivered low-birthweight infants.12,25,26 The National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network
study found that nearly 50% of pregnant African-American
women had bacterial vaginosis,17 similar to the rate
found in nonpregnant African American women in
NHANES.24
Recently, concerns have been raised that metronidazole,
the most common antibiotic used to treat bacterial
vaginosis, may increase preterm births in certain populations.
In studies that focus on treatment with metronidazole
(often at higher doses for treatment of Trichomonas
vaginalis), treated pregnant women were up to twice as
likely to have a preterm birth as their untreated counterparts.27,28 The juxtaposition of these data, along with
epidemiologic evidence associating bacterial vaginosis with
preterm birth, leads to considerable confusion for clinicians
and researchers alike. Whether to screen or treat multiple
times, when to start, and at what interval during pregnancy
are unanswered questions, as bacterial vaginosis may not
necessarily persist throughout pregnancy.
This review was conducted for the U.S. Preventive
Services Task Force (USPSTF) to update its 2001 recommendations29-31 by examining the chain of evidence
regarding the value of screening for and treating bacterial
vaginosis in reducing adverse pregnancy outcomes for
asymptomatic women at low, average, and high risk for
preterm delivery.
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Methods
Figure 1 presents the analytic framework and key
questions used to guide this updated review.
Data Sources
We searched the Cochrane Central Registry of Controlled
Trials, the Cochrane Database of Systematic Reviews,
and the Database of Abstracts of Reviews of Effects
to identify relevant studies through September 2007 (Appendix
Table 1 and Appendix Table 2). In addition, we conducted question-specific
searches in Ovid MEDLINE® for studies from 1996 to September
2007 and Ovid MEDLINE® Database of In-Process
and Other Non-Indexed Citations for studies from 2000
to September 2007 to identify otherwise nonindexed studies
relevant to any key question. We downloaded and
stored captured titles and abstracts in an EndNote database
for systematic review and tracking throughout the project.
We conducted additional targeted keyword searches and
compared the results with the existing database, reviewing unique citations relating to all key questions for inclusion.
We obtained additional articles by comparing reference
lists of other systematic reviews, individual studies, editorials,
reports, and Web sites and by consulting experts.
Study Selection
We included systematic reviews and individual randomized,
controlled trials that evaluated screening, treatment,
pregnancy outcomes, or adverse effects for asymptomatic
women with bacterial vaginosis. Two investigators
independently reviewed captured abstracts by using predefined
inclusion and exclusion criteria, and we retrieved
any title or abstract that either reviewer marked for inclusion.
Two reviewers also independently reviewed full-text
papers according to specific criteria. Investigators met to
resolve any discrepancies. For a screening trial to be included,
we required a comparison of pregnancy outcomes
for 2 distinct groups of women: 1 group was screened and
treated, and the other was unscreened. We defined asymptomatic
patients as those who presented for routine prenatal
visits and not specifically for evaluation of vaginal
discharge, odor, or itching. Under this definition, asymptomatic
patients could include both patients who had no
symptoms and those who were unaware of symptoms. We
felt this population was most reflective of that encountered
in everyday practice. Eligible studies were conducted in
settings where pregnant women went for prenatal and obstetric
care.
Study participants were categorized as having low,
average (general population), or high risk for preterm delivery.
Women who had not had a previous preterm delivery
or had no other risk factors for preterm delivery (for
example, nulliparous women) were considered to be low-risk.
The general population, or average-risk, category included
all pregnant women presenting to the clinic or
study site regardless of risk status. This would include a
mix of women at low, average, and high risk for preterm
delivery. Women who had a previous preterm delivery due
to spontaneous rupture of membranes or spontaneous preterm
labor were categorized as high-risk.
We excluded studies of nonpregnant women or those
symptomatic for bacterial vaginosis or other infections, as
well as studies lacking pregnancy outcomes, animal studies,
and non-English-language studies. We reviewed randomized,
controlled trials that matched all other criteria except
for including multiple infections to ascertain whether bacterial
vaginosis-only data were available for any pregnancy
outcome, and we excluded studies that only included outcome
data for multiple infections.
Data Extraction and Quality Assessment
Two independent reviewers read and extracted data on
study design, number of persons who enrolled in and completed
the study, setting, patient demographic characteristics,
inclusion and exclusion criteria, diagnostic methods,
and risk factors. We abstracted all pregnancy outcome data
provided. Preterm delivery (that is, the probability of delivery
before 37 weeks) may be further subdivided into
"spontaneous" preterm delivery and "indicated" preterm
delivery. Other abstracted outcomes included low birthweight
(defined as <2500 g); preterm, premature rupture
of membranes; preterm labor; spontaneous abortion; postpartum
endometritis; neonatal sepsis; and intrauterine,
neonatal, or perinatal death. We extracted treatment data
on reported gestational age at screening and treatment,
type of treatment, dose, regimen, administration route,
and number of treatment rounds. We documented and
summarized all data on adverse effects of treatment, including
drug tolerability, study discontinuation related to
drug effects, and adverse pregnancy outcomes. We applied
a "best-evidence" approach, in which studies with the highest
quality and most rigorous designs are emphasized.32
Two investigators separately evaluated the assessment
of relevance and appraisal of internal validity by using the
predefined study quality criteria of the USPSTF33
(Appendix Table 3) and the
Jadad34 rating systems for individual studies (Appendix
Table 4 and Appendix Table 5). Raters noted the appropriateness of procedures for
patient recruitment and selection, random assignment,
blinding, reporting of withdrawals and dropouts, and analyses.
Experts in the field suggested that we also abstract
study characteristics related to internal validity assessment
that are specific to this body of literature. These included
patient and provider blinding at second bacterial vaginosis
test and second round of treatment, timing and number of
dating sonograms obtained before or after random assignment,
and types and rates of coinfection. We assigned
studies with discrepant quality ratings to a third reviewer
and discussed them until we reached consensus. The overall
body of evidence for each key question is rated33 and
summarized35 in a systematic review used by the
USPSTF in making their recommendations for preventive
services.
Data Synthesis and Analysis
Meta-analysis
When appropriate, we performed a series of metaanalyses
that included new trials identified from this
search, as well as from studies identified from the previous
review, to estimate the effect of treatment on preterm delivery
(<37 weeks, <34 weeks, or <32 weeks); low birthweight;
and preterm, premature rupture of membranes.
The primary measure of effect of bacterial vaginosis treatment
was the absolute risk reduction, which is the difference
in proportions of these pregnancy outcomes between
the control and treatment group (control minus treatment).
We calculated the absolute risk reduction and its SE
for each study and used that as the measure of treatment
effect. An absolute risk reduction of zero indicated no
treatment effect or no difference between the treatment
and control groups for adverse pregnancy outcomes. A positive
absolute risk reduction favored treatment, indicating that women receiving treatment for bacterial vaginosis have
fewer adverse pregnancy outcomes, whereas a negative absolute
risk reduction favored placebo, indicating reduced
adverse pregnancy outcomes for those not being treated.
We stratified analyses by risk group (low, average, or
high) and pooled them separately to provide a combined
estimate of absolute risk reduction and its 95% CI for each
group. We used a random-effects model to account for
heterogeneity among studies.36,37 Estimates from a
random-effects model would be the same as those from a
fixed-effect model if no heterogeneity were found. We used
a standard chi-square test to test for heterogeneity and calculated
I2 statistics38 to quantify the magnitude of heterogeneity.
Substantial heterogeneity is evident when P is
less than 0.10 and I2 is greater than 50%. We did not pool
absolute risk reductions from the high-risk group studies,
because we considered the estimates to be too heterogeneous
owing to inconsistent treatment effects.
We performed a sensitivity analysis to address the effect
of study quality by excluding trials with a Jadad score
of 2 or less. Excluding the trial deemed weak for internal
validity did not change combined estimates. We also assessed
publication bias by using funnel plots and the Egger
linear regression method.39 No publication bias was
detected by these methods; however, their interpretation is
limited by the small number of trials.40 All analyses
were performed by using Stata, version 9.0 (Stata, College
Station, Texas).
Outcomes Table on Benefits and Harms
To provide a clinical interpretation of results, we used
data derived from the meta-analysis to construct an updated
projected outcomes table summarizing estimates of
the benefits and harms of screening for bacterial vaginosis
in 1000 women at high risk for preterm delivery. These
calculations include effect size data from the current meta-analyses
and other assumptions about the population of
interest (Appendix).
Role of the Funding Source
This research was funded by the Agency for Healthcare
Research and Quality under a contract to support the
work of the USPSTF. Agency staff and USPSTF members
participated in the initial scope of this work and reviewed
interim analyses and the final report. We distributed additional
reports to content experts for review. Agency approval
was required before this manuscript could be submitted
for publication, but the authors are solely
responsible for the content and the decision to submit it.
Return to Contents
Results
One hundred ninety-four full-text papers were retrieved
and screened for eligibility for all key questions.
Figure 2 details the search and selection process from the
initial title and abstract review, full-text review with reasons
for exclusion, and a final count of included studies for
each key question. Demographic, treatment, and outcome
data, as well as quality assessment information on included
studies, are found in Appendix Table 6. Typically, we excluded studies at the paper
level because of study design (not a randomized, controlled
trial) or sample (such as inclusion of symptomatic pregnant
women) or because data on multiple infections with bacterial
vaginosis were not separated from data on other infections.
Screening of Pregnant Women Who Are Asymptomatic
for Bacterial Vaginosis
We did not identify any studies that compared pregnancy
outcomes for women who are asymptomatic for bacterial vaginosis in a screened population versus a nonscreened
population.
Treatment of Pregnant Women Who Are Asymptomatic
for Bacterial Vaginosis
We found 8 systematic reviews and meta-analyses of
bacterial vaginosis treatment in pregnant women published
since the 2001 report.7,41-47 Because the inclusion
and exclusion criteria of the identified systematic reviews
and meta-analyses differed from our approach, we decided
to use these reviews as source documents only and retrieve
relevant, original articles studied in these papers. For example,
several reviews assessed studies as good-quality
when randomization methods or risk status of the women
were unknown, whereas other studies included co-infection
groups or symptomatic women.
Seven new randomized, controlled trials48-54 were
included in the area of treatment of asymptomatic pregnant
women with bacterial vaginosis (Appendix Table 6). All trials treated asymptomatic
pregnant women for vaginal syndromes, randomly assigned
women to treatment or placebo or no treatment,
and provided data for adverse pregnancy outcomes. Studies
were stratified by risk (low, average, or high) for preterm
delivery. Typically, author definition of risk level matched
that of the reviewers. All studies excluded symptomatic
women and women having a multiple pregnancy.
Treatment in Low-Risk Women
The previous review did not identify any low-risk
treatment trials, whereas our review identified 3 new randomized,
controlled trials48-50 that provided outcome
data for delivery before 37 weeks. Two trials in Finland48,49 screened women and treated them with 1 round of vaginal clindamycin before 17 weeks of gestation,
whereas the South African study50 administered 2
rounds of oral metronidazole later in pregnancy (400 mg
twice daily for 2 days at 15 to 25 weeks of gestation). Two
of the 3 studies reported co-infection; 1 had a bacteriuria
rate of approximately 12%, and showed no differences between
the treatment and control groups,50 and 1 had a
Chlamydia trachomatis rate of 3% and provided no details
on distribution relative to the treatment or placebo group.48 Meta-analyses of the 3 trials showed no effect of
treatment for delivery before 37 weeks (absolute risk reduction,
-0.019 [CI, -0.056 to 0.018]) (Figure 3) and no
significant heterogeneity (P = 0.57, I2 = 0%). The South
African study was the only study of the 3 to report on
delivery before 34 and 28 weeks and intrauterine, neonatal
or perinatal death, finding no effect.50 Details regarding
clinician knowledge of group allocation were not provided
for the South African trial,50 although in another study,49 a high random assignment refusal rate among bacterial
vaginosis-positive women was linked to knowledge of
diagnostic results. Overall, in reviewing these fair-quality
treatment trials, we found no evidence of clinical benefit
for treating low-risk pregnant women who are asymptomatic
for bacterial vaginosis.
Treatment in the General Population (Average-Risk Women)
We found 4 new treatment trials51-54 of women at
average risk for delivery before 37 weeks that met our inclusion
criteria and contributed additional pregnancy outcome
data to the original 2001 meta-analysis. These studies
are considered average risk because they are general
population studies that include a mix of women at low and
high risk for delivery before 37 weeks. All new trials administered
at least 1 round of treatment with 2% vaginal
clindamycin cream; 1 used 1 round only,51 2 administered
the same regimen for subsequent rounds,53,54
and 1 used oral clindamycin on the second round of treatment.52
Two population-based treatment trials screened a predominantly
white group of asymptomatic pregnant women
for bacterial vaginosis in Sweden54 or multiple infections
in Austria.52 In the largest of the trials,54 819
women in nonhospital clinics received a positive diagnosis
for bacterial vaginosis (Gram stain Nugent score, 6 to 10)
and then received either vaginal cream or no treatment. No
treatment benefit was demonstrated for delivery before 37
weeks (absolute risk reduction, -0.003 [CI, -0.024 to
0.019]).54 The other infection screening and treatment
program included screening for multiple vaginal abnormalities,
using a more liberal Gram stain Nugent score (4 to
10) to diagnose bacterial vaginosis in 297 women.52
Although the authors report that the treatment group had
significantly fewer births at 37 weeks than those who received
placebo, a post hoc analysis by infection type shows
that the main effect for treatment was due to candidiasis,
not bacterial vaginosis (absolute risk reduction for data on
bacterial vaginosis only, 0.022 [CI, -0.025 to 0.070]).
Two additional average-risk bacterial vaginosis treatment
trials in the United Kingdom53 and Italy51
report differential treatment effects for delivery before 37
weeks in bacterial vaginosis-positive women treated with
2% clindamycin cream. Lamont and colleagues' well-executed
hospital clinic trial of 409 women in the United
Kingdom at 13 to 20 weeks of gestation reports on a sample
comprising 70% white and 15% black women.53
This is the only trial we reviewed in which caregivers and
patients were blinded for both rounds of treatment. The
women who received treatment were less likely than those
who received placebo to deliver before 37 weeks (absolute
risk reduction, 0.055 [CI, 0.003 to 0.108]).53 The average-risk trial from Italy showed no difference in delivery
before 37 weeks (absolute risk reduction, 0.034 [CI, -0.101
to 0.170]); however, the study has considerable threats to internal
validity:51 Randomization methods were not standard
or well described, women and caregivers were not
blinded, and concurrent vaginal syndromes were likely.
An updated meta-analysis pooling the new average-risk
treatment trials51-54 with those reviewed in 200155-58 showed no treatment benefit for delivery before 37
weeks (absolute risk reduction, 0.006 [CI, .0.009 to
0.022]), and no significant heterogeneity was detected
(P = 0.36, I2 = 9.6%) (Figure 3). Excluding the trial we
deemed weak for internal validity51 did not change
combined estimates (Figure 3 ).
Only 1 new average-risk study explored delivery before
34 weeks and before 32 weeks; no statistically significant
results were found.54 When combined with the 2 studies56-57
from the previous report, pooled data reveal no
treatment effect for delivery before 32 weeks (absolute risk
reduction, 0.001 [CI, .0.008 to 0.010]) (Figure 4).
Newly identified average-risk trials reported conflicting results
for low birthweight,51,53,54 and when combined
with the studies in the 2001 report (55-58), the pooled
estimate for the 7 trials showed no effect of treatment for
low birthweight (absolute risk reduction, 0.000 [CI,
.0.018 to 0.018]) (Figure 5). Again, no significant heterogeneity
was detected (P = 0.16; I2 = 35%), and excluding
the trial with compromised internal validity did not change
combined estimates. For the outcome of preterm, premature
rupture of membranes, 1 new average-risk trial51
reported a trend toward an adverse effect of treatment;
however, it was not statistically significant. When combined
with the previously reviewed studies for this outcome,55,57,58 pooled results indicated no treatment
effect (absolute risk reduction, .0.006 [CI, .0.030 to
0.018]) (Figure 5).
We found several issues related to threats to internal
validity that were common to the new average-risk trials,
especially where blinding was not apparent or was clearly
not achieved.51,52,54 Only 1 study53 reported
blinding of care providers and patients throughout the study; the investigators administered placebo cream on
both rounds of treatment. Lamont and colleagues' study53 was the only new study to show a treatment effect for
any pregnancy outcome (delivery <37 weeks), and pooled
results for all outcomes showed no treatment effects. The
definition of bacterial vaginosis or abnormal vaginal flora
also varied in these studies; however, findings confirm the
results of the previous review, showing no pooled treatment
effects for any adverse pregnancy outcomes in
women who are asymptomatic for bacterial vaginosis in the
general population.30 Similar to women at low risk for
preterm delivery, the general population seems to lack any
clear clinical benefit from screening and treatment for
asymptomatic bacterial vaginosis during pregnancy.
Treatment in High-Risk Women
We identified 1 new study50 since the 2001 report
that recruited pregnant women with a history of preterm
labor or midtrimester miscarriage who were at high risk for
delivery before 37 weeks. In hospital clinics in South Africa,
127 asymptomatic women (86% unmarried; mean
age, 27.5 years) at 15 to 26 weeks of gestation who tested
positive for bacterial vaginosis were treated with up to 2
rounds of oral metronidazole (400 mg twice daily for 2
days) or 100 mg of vitamin C placebo. Bacterial vaginosis
persisted in 30% of the treatment group that was positive
for bacterial vaginosis, and an additional 2-day regimen of
metronidazole was provided. Findings reveal a significant
adverse effect of treatment on delivery before 37 weeks,
indicating that treatment of bacterial vaginosis increased
the chance of preterm delivery (absolute risk reduction,
-0.193 [CI, -0.358 to -0.029]).50 We did not pool
the results with data from the 2001 report because of substantial
heterogeneity among the trials (P = 0.001; I2 =
82%) and inconsistency in the direction of effects. In
short, 3 studies in high-risk women showed benefit,58-60 1 reported significant harm50, and 1 reported no
benefit (Figure 3).57 Go to Table 1 for detailed abstraction
of these studies.
The new high-risk trial also provides data for the outcome
of delivery before 34 weeks, showing no treatment
effect (absolute risk reduction, -0.125 [CI, -0.259 to
0.009]).50 Pooling the outcome data for delivery before
34 weeks from the new trial50 with the data from the
high-risk studies in the 2001 report57-59,61 indicates
no significant treatment effect (absolute risk reduction,
0.006 [CI, -0.067 to 0.079]) (Figure 4). We found no
significant heterogeneity for this outcome (P = 0.22; I2 =
30%). Data for low birthweight and preterm, premature
rupture of membranes were not available for the new highrisk
study.50 We found statistically significant heterogeneity
among the trials identified for the 2001 report for
both low birthweight (P = 0.042; I2 = 69%) and preterm,
premature rupture of membranes (P = 0.001; I2 = 86%); for this reason, and because of the inconsistent harmful
and beneficial treatment effects, we did not pool the results
for these 2 outcomes (Figure 5).
Summary of Benefits and Harms
We developed an outcomes table (Table 2) to provide
an updated clinical interpretation of results for the
USPSTF. In looking at the high-risk group, we used
data derived from the meta-analysis50,57-60 and
specific assumptions to approximate the benefits and
harms of screening for bacterial vaginosis in 1000
women at high risk for preterm delivery. Estimates are
from studies with a baseline preterm delivery rate of less
than 30%50,57 for the general high-risk group and
greater than 30%58-60 for the more selected highrisk
group. These projections suggest that although a
subgroup of high-risk women may benefit from screening
and treatment for bacterial vaginosis in pregnancy, a
sizeable group would receive either no benefit or may
experience harm. The Appendix provides outcomes table methodology, and
the Appendix Figure
shows how the calculations were performed.
In the general high-risk population of 1000 women
screened, 238 would receive a correct diagnosis of bacterial
vaginosis (assuming 95% accuracy of diagnostic
testing), and 190 of these women would successfully
complete therapy (assuming 80% adherence). Given
these assumptions, we calculate that screening and treating
for bacterial vaginosis would result in 24 additional
deliveries before 37 weeks (CI, 2 to 45 additional deliveries);
7 additional cases of preterm, premature rupture
of membranes (CI, 8 fewer to 22 additional cases); and
7 additional deliveries before 34 weeks (CI, 11 fewer to
25 additional deliveries). Given the data and assumptions
for the more selected high-risk group, projections
show that screening and treatment would result in an
estimated 44 fewer deliveries before 37 weeks (CI, 22 to
64 fewer deliveries); 45 fewer cases of preterm, premature
rupture of membranes (CI, 22 to 68 fewer cases);
and 13 fewer cases of delivery before 34 weeks (CI, 33
fewer to 7 additional cases) per 1000 women screened.
These findings are consistent with conclusions from the
2001 report.
For the most adverse outcomes, sensitivity analyses
show that the accuracy of a reasonable screening test did
not change the conclusion of the projected outcomes table.
For example, assuming a sensitivity of 80% (instead of
95% as in the above example) for the general high-risk
population, screening and treatment results in 20 additional
deliveries before 37 weeks (CI, 2 to 38 additional
deliveries) and 6 additional cases of preterm, premature
rupture of membranes (CI, 7 fewer to 18 additional cases),
compared with 24 and 7 additional cases, respectively. Because
we assumed a potential increase in delivery before 34
weeks in bacterial vaginosis-negative patients who received
treatment, on the basis of data from Hauth and colleagues,60 the effect of screening on delivery before 34 weeks is
moderately sensitive to changes in the accuracy of the
screening test. For example, in the more selected high-risk
group, we estimate that screening and treatment would
result in only 7 fewer cases (CI, 27 fewer to 13 additional
cases) of delivery before 34 weeks if the specificity of the
screening test for bacterial vaginosis is 80%, compared
with 13 fewer cases at a specificity of 95%.
Adverse Effects of Screening or Treatment
We found no studies that directly addressed the adverse
effects of screening pregnant women who are asymptomatic
for bacterial vaginosis. However, the effects of treatment
on women who received an incorrect diagnosis of
bacterial vaginosis can provide information on the effect of
false-positive test results. None of the 7 new treatment trials
included in this review provides data on bacterial vaginosis-negative women receiving treatment. In 2 studies identified in
the previous review, bacterial vaginosis-negative women who
received antibiotics had more deliveries before 34 weeks than
those not given antibiotics; this was statistically significant in 1
study61 and borderline statistically significant in the other.60
In addition, 1 study reported a statistically significantly
greater frequency of neonatal sepsis.61
One of the 7 treatment trials identified and screened
for adverse effects showed an adverse treatment effect for
women at high risk for preterm delivery. As noted earlier,
asymptomatic pregnant women with a history of preterm
labor or midtrimester miscarriage who received
metronidazole had a greater chance of preterm delivery
than those who received a vitamin C placebo.50 None
of the other trials showed statistically significant adverse
effects for pregnancy outcomes due to treatment. Adverse
effects in the form of treatment tolerability or side
effects varied. One study52 stated that no patients
reported adverse reactions to vaginal cream, whereas 3
studies49,50,53 did not report any data on adverse
tolerability effects. A trial of vaginal clindamycin reported
adverse treatment effects in the form of 3 patient
withdrawals due to persistent vulvovaginal itching54,
whereas another trial48 reported that this side effect
occurred with similar frequency in treatment (3.21%)
and placebo groups (3.19%).
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