An Update Review for the U.S. Preventive Services Task Force (continued)
Discussion
Preterm birth rates have increased in the past decade,62 and strong epidemiologic evidence has suggested an association between bacterial vaginosis and preterm birth.
After decades of research and with heightened awareness of
measuring potential adverse effects of medications, evidence
is emerging that the drug being used to treat bacterial
vaginosis may, at some doses and for some populations,
be triggering adverse pregnancy outcomes. At the same
time, evidence suggests that inherent differences in populations,
such as previous pregnancy complications, gestational
age, ethnicity, or co-infection, may also influence
which women are helped or harmed by screening and
treatment for bacterial vaginosis. New treatment trial data
pooled with 2001 report data showed no benefit to screening
and treating women who are asymptomatic for bacterial
vaginosis if they had a low or average risk for preterm
delivery for the outcomes of delivery before 37, 34, or 32
weeks; preterm, premature rupture of membranes; or low
birthweight. Results from the studies of women at high risk
for preterm delivery are heterogeneous and conflicting. For
the outcome of delivery before 37 weeks, 3 of the 5 trials
reported a significant treatment benefit, 1 showed significant
treatment harm, and 1 showed no benefit (Figure 3).
Other reviews have similarly reported no treatment effect
for low-risk asymptomatic pregnant women with bacterial
vaginosis but suggest a potential but unclear benefit of
treatment for some patients at high risk for preterm delivery.7,44,45
Although additional studies of women at high risk for
preterm delivery are required to meaningfully explore heterogeneity
in a meta-regression, we did examine each study
for factors that may explain the variation in treatment response
and potentially guide future research (Table 1).
One of the clear differences among studies was the variation
in baseline preterm delivery rates in the placebo
group. It would have been helpful to know the overall
preterm birth rate for the clinics in which the studies were
conducted because this would allow the greatest opportunity
for clinicians to apply results to their own practices.
However, because these data were not available for most
studies, we documented the preterm delivery rate in the
group of bacterial vaginosis–positive women receiving placebo.
Studies reporting a baseline risk greater than 30% for
delivery before 37 weeks in their bacterial vaginosis–positive
placebo groups favored treatment, whereas those with
a risk less than 30% favored placebo (Figure 3). Although
they were conducted in different countries, the new high-risk
trial50 is most similar to the best-quality high-risk
trial identified in the 2001 report:57 Approximately
23% of women positive for bacterial vaginosis in groups
receiving placebo delivered before 37 weeks. The study in
the 2001 report indicated a trend toward treatment harm
for delivery before 37 weeks,57 and the new trial indicated
statistically significant harm from treatment for this
outcome.50 Although ethnicity is suggested as a potential
factor playing a role in both bacterial vaginosis and
preterm birth, our data from predominantly minority samples
show disparate treatment results;57,60 reporting of
race data is scarce in other trials. The detailed description
of these studies do not clearly indicate which factors may
explain the differences in preterm delivery rates or, potentially,
the association of treatment effect; however, both
raise concerns about the unintended potential for harm.
In addition, the methodological differences among
studies could have led to conflicting results. Several methodological
challenges arose in synthesizing this body of literature.
Only 1 study provided details on blinding procedures
throughout the study. Most of the trials did not
report whether the women or caregivers continued to be
blinded to their group allocation upon re-treatment. The
potential to violate intention-to-treat by modifying the estimate
of gestational age after random assignment and
treatment is another weakness in study design, especially if
this estimate were changed differentially in the treatment
and control groups: Bias would exist if treatment were associated
with a change in the gestational age estimate.
However, few studies provided sufficient data on sonography
timing to evaluate this factor. In addition, varying
definitions of bacterial vaginosis, along with the reporting
ambiguity of multiple infection status, make it difficult to
meaningfully combine this research. More detailed information
on these factors would create greater opportunities
to assess both the contributions and potential biases of the
studies.
Metronidazole treatment has been associated with adverse
pregnancy outcomes in certain subgroups. However,
studies to date of bacterial vaginosis in asymptomatic pregnant
women have not provided sufficient numbers or details
to identify the specific factors playing the most prominent
role for harms or benefits. Clinicians need to remain
vigilant to the potential harmful effects of bacterial vaginosis
treatments, because no screening test is 100% accurate.
Researchers are in an uncomfortable position of uncertainty,
balancing the ethics of continuing potentially risky
investigations with the possibility of substantial benefit.
Only when multiple, well-executed studies consistently
point to the same subgroups showing benefits or harms
does confidence increase that such differences are real.62
More research is needed to better understand these groups
and the conditions under which treatment can be harmful
or helpful and to explore relevance to other adverse pregnancy
outcomes, including preterm delivery before 34
weeks.
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Notes
Current Author Addresses
Peggy Nygren, MA: Oregon Heath & Science University, 3181 SW Sam Jackson Road, Portland, OR 97239.
Rongwei Fu, PhD: Oregon Health & Science University, 3181
SW Sam Jackson Road, Portland, OR 97239
Michele Freeman, MPH: Oregon Health & Science University, 3181
SW Sam Jackson Road, Portland, OR 97239
Christina Bougatsos, BS: Oregon Health & Science University, 3181
SW Sam Jackson Road, Portland, OR 97239
Mark Klebanoff, MD, MPH:National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Boulevard, Room 7B05F, MSC 7510, Bethesda, MD 20892
Jeanne-Marie Guise, MD, MPH: Oregon Health & Science University, 3181
SW Sam Jackson Road, Portland, OR 97239
Disclaimer
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.
Potential Conflicts of Interest
No investigators have any affiliations or financial involvement (e.g., employment, consultancies, honoraria, stock options, expert testimony, rants or patents received or pending, or royalties) that conflict with material presented in this article.
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Source: Nygren P, Fu R, Freeman M, Bougatsos C, Klebanoff M, Guise JM. Evidence on the benefits and harms of screening and treating pregnant women who are asymptomatic for bacterial vaginosis: an update review for the U.S. Preventive Services Task Force. Ann Intern Med 2008;148(3):220-33.
Acknowledgment
The authors thank Andrew Hamilton, MLS, MS, for
conducting the literature searches, and USPSTF leads Kimberly Gregory,
MD, MPH, Lucy Marion, PhD, RN, and Diana Petitti, MD, MPH,
and AHRQ officers Iris Mabry, MD, MPH and Mary Barton, MD,
MPP, for their guidance on this project.
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Current as of February 2008
Internet Citation:
Nygren P, Fu R, Freeman M, Bougatsos C, Klebanoff M, Guise JM. Evidence on the Benefits and Harms of Screening and Treating Pregnant Women Who Are Asymptomatic for Bacterial Vaginosis: An Update Review for the U.S. Preventive Services Task Force. February 2008. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/uspstf08/bv/bvup.htm
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