Screening for Bacterial Vaginosis in Pregnancy to Prevent Preterm Delivery: Recommendation Statement

Am Fam Physician. 2008;78(1):106-110

This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations and supporting scientificevidence on screening for bacterial vaginosis in pregnancy to prevent preterm delivery. See Table 1 for a description of the USPSTF grades and Table 2 for a description of USPSTF classification of levels of certainty regarding net benefit. The complete information on which this statement is based, including evidence tables and references, is included in the evidence synthesis¹ on this topic, available on the USPSTF Web site at http://www.uspreventiveservicestaskforce.org.

Grade	Grade definition	Suggestions for practice
A	The USPSTF recommends the service. There is high certainty that the net benefit is substantial.	Offer/provide this service.
B	The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.	Offer/provide this service.
C	The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is moderate or high certainty that the net benefit is small.	Offer/provide this service only if there are other considerations in support of offering/providing the service in an individual patient.
D	The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.	Discourage the use of this service.
I	The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality or conflicting, and the balance of benefits and harms cannot be determined.	Read “Clinical Considerations” section of USPSTF Recommendation Statement. If offered, patients should understand the uncertainty about the balance of benefits and harms.

Level of Certainty	Description
High	The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies
Moderate	The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as: the number, size, or quality of individual studies inconsistency of findings across individual studies limited generalizability of findings to routine primary care practice lack of coherence in the chain of evidence
Moderate	As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion
Low	The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of: the limited number or size of studies important flaws in study design or methods inconsistency of findings across individual studies gaps in the chain of evidence findings not generalizable to routine primary care practice a lack of information on important health outcomes
Low	More information may allow an estimation of effects on health outcomes

For a clinical summary of this recommendation statement, see Table 3, or go to http://www.ahrq.gov/clinic/uspstf08/bv/bvsum.htm. The recommendation is also posted on the Web site of the National Guideline Clearinghouse at http://www.guideline.gov.

Population	Asymptomatic pregnant without risk women factors for preterm delivery delivery		Asymptomatic pregnant women with risk factors for preterm
Recommendation	Do not screen Grade: D*		No recommendation due to insufficient evidence

The USPSTF makes recommendations about preventive care services for patients without recognized signs or symptoms of the target condition. It bases its recommendations on a systematic review of the evidence of the benefits and harms and an assessment of the net benefit of the service.

The USPSTF recognizes that clinical or policy decisions involve more considerations than this body of evidence alone. Physicians and policy makers should understand the evidence, but individualize decision making to the specific patient or situation.

Summary of Recommendations and Evidence

The USPSTF recommends against screening for bacterial vaginosis in asymptomatic pregnant women at low risk for preterm delivery. D recommendation.

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for bacterial vaginosis in asymptomatic pregnant women at high risk for preterm delivery. I statement.

Rationale

Importance. The associations between bacterial vaginosis and adverse pregnancy outcomes, such as preterm delivery, are well documented.

Detection. Good-quality evidence indicates that screening tests (the Amsel clinical criteria or Gram stain) can detect bacterial vaginosis.

Benefits of Detection and Early Intervention. Asymptomatic Pregnant Women at Low Risk for Preterm Delivery: No direct evidence indicates that screening for bacterial vaginosis reduces adverse health outcomes in asymptomatic pregnant women at low risk for preterm delivery. Good evidence indicates that treatment of bacterial vaginosis in these women lacks benefit.

Asymptomatic Pregnant Women at High Risk for Preterm Delivery: No direct evidence indicates that screening for bacterial vaginosis reduces adverse health outcomes in asymptomatic pregnant women at high risk for preterm delivery. Evidence from good-quality studies is conflicting with respect to the benefits of treating bacterial vaginosis.

Harms of Detection and Early Treatment. Asymptomatic Pregnant Women at Low Risk for Preterm Delivery: Evidence is poor (because studies are lacking) for harms of screening for bacterial vaginosis in asymptomatic pregnant women at low risk for preterm delivery. Evidence is fair that false-positive results from screening lead to harms from treatment.

Asymptomatic Pregnant Women at High Risk for Pre-term Delivery: Evidence is poor (because studies are lacking) for harms of screening for bacterial vaginosis in asymptomatic pregnant women at high risk for preterm delivery. Studies on the harms of treatment have conflicting results.

USPSTF Assessment. The USPSTF concludes that for asymptomatic pregnant women at low risk for preterm delivery, there is moderate certainty that screening for bacterial vaginosis has no net benefit.

The USPSTF concludes that for asymptomatic pregnant women at high risk for preterm delivery, the evidence is conflicting and the balance of benefits and harms cannot be determined.

Clinical Considerations

Patient Population. This recommendation addresses screening for bacterial vaginosis in asymptomatic pregnant women.
Risk Assessment. Several factors have been associated with increased risk for preterm delivery. All of these associations are small to moderate. These factors include, but are not limited to, African-American race or ethnicity, body mass index less than 20 kg per m², previous preterm delivery, vaginal bleeding, a short cervix (less than 2.5 cm), pelvic infection, and bacterial vaginosis. These factors can act in isolation or in combination. Furthermore, bacterial vaginosis in pregnancy is more common among African-American women, women of low socioeconomic status, and those who have previously delivered low–birth-weight infants. For the purpose of the current recommendation, women were considered to be at low risk if they had no previous preterm delivery or other risk factors for preterm delivery (often these were nulliparous women). Women were considered to be at high risk if they had a previous preterm delivery.
Screening Tests. Bacterial vaginosis is diagnosed by using the Amsel clinical criteria or Gram stain. With the Amsel criteria, the clinical diagnosis is made by fulfilling three of four criteria: vaginal pH greater than 4.7, the presence of clue cells on wet mount, thin homogeneous discharge, and amine “fishy odor” when potassium hydroxide is added to the discharge.
Suggestions for Practice. This recommendation statement addresses screening for bacterial vaginosis in asymptomatic women. Treatment of symptomatic cases should be based on the clinical situation.
Treatment. Oral metronidazole (Flagyl) and oral clindamycin (Cleocin), as well as vaginal metronidazole gel or clindamycin cream, are used to treat bacterial vaginosis. The optimal treatment regimen for pregnant women with bacterial vaginosis is unclear. Refer to the Centers for Disease Control and Prevention (CDC) Web site for current treatment recommendations: http://www.cdc.gov/std/treatment/2006/vaginal-discharge.htm#vagdis2.

Other Considerations

RESEARCH NEEDS

There are several evidence gaps in the literature on screening and treating bacterial vaginosis in asymptomatic pregnant women. A critical gap in the evidence exists in demonstrating a benefit of treatment in asymptomatic pregnant women at increased risk for preterm delivery. Available evidence on treatment benefit is conflicting. Additional research is needed to evaluate the benefit of screening and treating asymptomatic bacterial vaginosis in women at highest risk for preterm delivery. Research is also needed to assess which screening tests physicians use to diagnose bacterial vaginosis in clinical practice and the accuracy of these tests. Finally, continued research is needed to determine the optimal treatment regimen for bacterial vaginosis.

Discussion

Burden of Disease. Bacterial vaginosis is the most common lower genital tract syndrome among women of reproductive age. It involves an imbalance in the vaginal bacterial ecosystem, with a decrease in hydrogen peroxide–producing lactobacilli and an increase in Gardnerella vaginalis, anaerobes, and mycoplasmas. Studies have documented an association between bacterial vaginosis and the adverse pregnancy outcome of preterm delivery. This epidemiologic evidence has been used as a rationale for screening asymptomatic pregnant women for bacterial vaginosis.

The literature demonstrates a prevalence of bacterial vaginosis ranging from 9 to 23 percent in studies conducted in academic medical centers or public hospitals.¹ The prevalence of bacterial vaginosis in pregnant women in community clinical settings is not well studied. Bacterial vaginosis in pregnancy is more common among African-American women, women of low socioeconomic status, and women who have previously delivered low–birth-weight infants.

The natural history of bacterial vaginosis in pregnant women has shown that up to 50 percent of cases resolve spontaneously during pregnancy.¹ Because bacterial vaginosis may not continue throughout pregnancy, whether to screen and treat multiple times, and optimal screening intervals, are not known.¹

Scope of Review. The USPSTF updated its 2001 recommendation on bacterial vaginosis. The goal was to review the literature and to identify new evidence addressing previously identified gaps, such as the characterization of patients most likely to benefit from screening and the optimal timing of screening and treatment on pregnancy outcomes.

Accuracy of Screening Tests. Bacterial vaginosis is diagnosed by using the Amsel clinical criteria or Gram stain. The reliability of the Amsel clinical criteria in community practice is unknown. Gram stain of vaginal discharge may be a more reliable means of diagnosing bacterial vaginosis, and it offers the added ability to quantify and classify bacterial load. As a result, Gram stain has been the primary means used to diagnose bacterial vaginosis in research studies. However, Gram stain is less commonly used in clinical practice because of the need for laboratory facilities and the delay in receiving diagnostic results.¹

No studies of diagnostic assessment in the clinical practice setting were found in the literature. Most studies compared the application of all Amsel clinical criteria with Gram stain in a research setting. In the 2001 USPSTF review, comparisons of the Amsel clinical criteria with Gram stain yielded sensitivities from 62 to 97 percent and specificities from 66 to 95 percent, with Gram stain as the criterion standard in diagnosing bacterial vaginosis.²

The 2001 USPSTF evidence review stated that the preferred screening test would predict pregnancy outcomes with the most accuracy. The current update identified studies that evaluated diagnostic tests in predicting preterm birth.¹ A poor-quality meta-analysis (11 studies) showed no difference in accuracy between clinical criteria and Gram stain in preterm delivery.³

Effectiveness of Early Detection and Treatment. Because the evidence is poor, there is no known benefit of early detection in either low-risk or high-risk, asymptomatic pregnant women.

The USPSTF found good evidence of a lack of benefit from treatment in low-risk, asymptomatic pregnant women. Data from randomized clinical trials of good quality pooled with 2001 report data showed no treatment effects for asymptomatic women at low risk for preterm delivery at less than 37 weeks.¹

Randomized, controlled trials of good quality had conflicting results about treatment benefit in high-risk, asymptomatic pregnant women. There was statistically significant heterogeneity among the trials (P < .001). Three of the five trials reported a statistically significant benefit from treatment, one showed a statistically significant harm from treatment, and one showed no benefit.^4–8

Potential Harms of Screening and Treatment. No studies directly addressed the harms of screening (for example, increased risk for preterm delivery). The effects of treatment in women with a misdiagnosis of bacterial vaginosis have been indirectly studied and were documented in the 2001 review.² Two studies compared women who tested negative for bacterial vaginosis and were treated with women who tested negative and were not treated. The studies found an increase in preterm delivery at less than 34 weeks in the group who tested negative and were treated.^7,9 A recent study also confirmed the potential harm of misdiagnosis (greater spontaneous preterm delivery at less than 37 weeks) in women who tested negative for bacterial vaginosis and were treated versus the placebo group, but this finding did not reach statistical significance.¹⁰

Estimate of Magnitude of Net Benefit. In low-risk, asymptomatic pregnant women, the USPSTF found no known benefits of detection and early treatment and concluded with moderate certainty that screening has no net benefit. Given the lack of net benefit, the USPSTF recommends against routine screening for bacterial vaginosis in low-risk, pregnant women. The results of studies assessing bacterial vaginosis treatment in high-risk, asymptomatic pregnant women are conflicting. As a result of this significant evidence gap, the USPSTF concluded that the evidence is insufficient to make a recommendation about screening for bacterial vaginosis in high-risk pregnant women.

Recommendations from Other Groups

The CDC,¹¹ the American College of Obstetricians and Gynecologists,¹² the Cochrane Pregnancy and Childbirth Group,¹³ the British Association for Sexual Health and HIV (BASHH)/Clinical Effectiveness Group,¹⁴ and the American Academy of Family Physicians (AAFP)¹⁵ make similar recommendations about screening and treatment of pregnant women with bacterial vaginosis. All recommend against routine screening for bacterial vaginosis in asymptomatic pregnant women. With respect to women at high risk for preterm delivery, the CDC, American College of Obstetricians and Gynecologists, the AAFP, and BASHH state that there may be high-risk women for whom screening and treatment may be beneficial. The CDC does not recommend the use of clindamycin vaginal cream in the second half of pregnancy.

Nygren P, Fu R, Freeman M, Bougatsos C, Guise JM. Screening and treatment for bacterial vaginosis in pregnancy: systematic review to update the 2001 U.S. Preventive Services Task Force Recommendation Statement. Evidence synthesis no. 57. Rockville, Md.: Agency for Healthcare Research and Quality. http://www.ahrq.gov/clinic/uspstf08/bv/bves.pdf. Accessed March 31, 2008.

Guise JM, Mahon SM, Aickin M, Helfand M, Peipert JF, Westhoff C. Screening for bacterial vaginosis in pregnancy. Am J Prev Med. 2001;20(3 suppl):62-72.

Honest H, Bachmann LM, Knox EM, Gupta JK, Kleijnen J, Khan KS. The accuracy of various tests for bacterial vaginosis in predicting preterm birth: a systematic review. BJOG. 2004;111(5):409-422.

Carey JC, Klebanoff MA, Hauth JC, et al. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med. 2000;342(8):534-540.

Odendaal HJ, Popov I, Schoeman J, Grové D. Preterm labour—is Mycoplasma hominis involved?. S Afr Med J. 2002;92(3):235-237.

McDonald HM, O'Loughlin JA, Vigneswaran R, et al. Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial. Br J Obstet Gynaecol. 1997;104(12):1391-1397.

Hauth JC, Goldenberg RL, Andrews WW, DuBard MB, Copper RL. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med. 1995;333(26):1732-1736.

Morales WJ, Schorr S, Albritton J. Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am J Obstet Gynecol. 1994;171(2):345-347 ; discussion 348–349.

Vermeulen GM, Bruinse HW. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial. Br J Obstet Gynaecol. 1999;106(7):652-657.

Andrews WW, Goldenberg RL National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. What we have learned from an antibiotic trial in fetal fibronectin positive women. Semin Perinatol. 2003;27(3):231-238.

Centers for Disease Control and Prevention (CDC). Sexually transmitted disease treatment guidelines 2006—diseases characterized by vaginal discharge. http://www.cdc.gov/std/treatment/2006/vaginal-discharge.htm#vagdis2. Accessed March 31, 2008.

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. (Replaces Technical Bulletin number 206, June 1995; Committee Opinion number 172, May 1996; Committee Opinion number 187, September 1997; Committee Opinion number 198, February 1998; and Committee Opinion number 251, January2001). Obstet Gynecol. 2001;98(4):709-716.

McDonald H, Brocklehurst P, Gordon A. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. 2007(1).

British Association for Sexual Health and HIV and the Clinical Effectiveness Group. National guideline for the management of bacterial vaginosis (2006). http://www.bashh.org/guidelines/2006/bv_final_0706.pdf. Accessed March 31, 2008.

American Academy of Family Physicians. Recommendations for clinical preventive services—bacterial vaginosis. https://www.aafp.org/patient-care/clinical-recommendations/all/bacterial-vaginosis.html. Accessed March 31, 2008.