Final Research Plan

Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: Screening

May 17, 2018

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Expand All
Panel 1

The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from February 22 until March 21, 2018 at 5:00 p.m., ET.

This figure is the analytic framework depicting the five key questions and the research approach that will guide the evidence review outlined in this research plan. In general, the figure illustrates the overarching and first key question of whether screening for bacterial vaginosis leads to reduced preterm delivery and related morbidity and mortality outcomes. The framework starts on the left and follows the intervention pathway for the population of interest, namely asymptomatic pregnant adolescents and women. Moving from left to right, the second key question examines the effect of screening on the diagnosis of bacterial vaginosis, and the third evaluates whether any harms result from such screening. The fourth key question examines whether treating bacterial vaginosis leads to reduced preterm delivery and related morbidity and mortality outcomes, and the fifth evaluates whether any harms result from such treatment.

Abbreviation: KQ=key question.

  1. Does screening for bacterial vaginosis in asymptomatic pregnant adolescents and women reduce preterm delivery and related morbidity and mortality?
    1. Does the effect of screening vary by baseline risk (e.g., low- vs. high-risk) for preterm delivery?
    2. Does the effect of screening vary by race/ethnicity?
    3. Does the effect of screening vary by maternal age?
    4. Does the effect of screening vary by gestational age?
    5. Does the effect of screening vary by other risk factors for preterm delivery (e.g., coinfection with sexually transmitted infections, HIV status)? 
  2. What is the diagnostic accuracy of tests used to screen for bacterial vaginosis? 
    1. Does diagnostic accuracy vary by pregnancy status?
  3. What are the harms of screening for bacterial vaginosis in asymptomatic pregnant adolescents and women?
  4. Does treatment of bacterial vaginosis during pregnancy reduce preterm delivery and related morbidity and mortality? 
    1. Does the effect of treatment vary by baseline risk (e.g., low- vs. high-risk) for preterm delivery?
    2. Does the effect of treatment vary by race/ethnicity?
    3. Does the effect of treatment vary by maternal age?
    4. Does the effect of treatment vary by gestational age?
    5. Does the effect of treatment vary by other risk factors for preterm delivery (e.g., coinfection with sexually transmitted infections, HIV status)
  5. What are the harms of treatment of bacterial vaginosis in pregnant adolescents and women?
    1. What are the harms of treatment to pregnant adolescents and women?
    2. What are the harms of treatment to the fetus or newborn?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the association between bacterial vaginosis, abnormal vaginal flora, or intermediate flora and preterm delivery in U.S. populations (or in similar populations if U.S. data are not available or are limited)? 
  2. Is treatment of abnormal vaginal flora and intermediate flora associated with reduced preterm delivery?
  3. What is the association between bacterial vaginosis and other known risk factors for preterm delivery?
  4. What is the uptake or use of various diagnostic tests for bacterial vaginosis in clinical practice?
  5. What are the adverse drug events related to metronidazole or clindamycin when used to treat bacterial vaginosis in nonpregnant adolescents and women?

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).

  Include Exclude
Population KQs 1, 3: Asymptomatic pregnant adolescents and women; studies that include mixed populations of symptomatic and asymptomatic participants will be included if the results for asymptomatic participants are reported separately or if less than 20% of the study population is characterized as symptomatic for bacterial vaginosis

KQ 2: Adolescents and women of reproductive age, including pregnant or nonpregnant study participants

KQs 4, 5: Pregnant adolescents and women diagnosed with bacterial vaginosis

 KQs 1, 3, 4, 5: Nonpregnant adolescents and women

KQs 1, 3: Adolescents and women with symptomatic bacterial vaginosis
Intervention KQs 1, 3: Routine screening for bacterial vaginosis using Gram stain or any tests listed under KQ 2

KQ 2: Screening interventions:

  • Clinical assessment using complete or partial Amsel criteria
  • BD MAX™ Vaginal Panel
  • BD Affirm™ VPIII Microbial Identification Test
  • Colorimetric assessment of pH
  • VS-SENSE PRO™ (pH indicator vaginal swab)
  • OSOM® BVBLUE® (detects sialidase activity)
  • Other tests*

KQs 4, 5: Treatment interventions (oral or vaginal):

  • Metronidazole
  • Clindamycin
 KQ 1: Screening for multiple organisms or infections if the effect of screening specifically for bacterial vaginosis cannot be isolated

KQ 2: Tests for diagnosis of bacterial vaginosis that are obsolete or no longer being marketed

KQs 4, 5: Treatment interventions:

  • Treatments not evaluated in pregnant women
  • Interventions that are not approved by the U.S. Food and Drug Administration for treatment of bacterial vaginosis:
    • Rifamixin
    • Dequalinium chloride
    • Oral or vaginal probiotics
    • Topical antiseptics
  • Treatment of partner (as sole strategy)
Comparison KQ 1: No screening, usual care

KQ 2: Screening reference standards:

  • Gram stain (based on Nugent criteria)
  • Clinical assessment using complete Amsel criteria

KQs 4, 5: Treatment interventions:

  • Placebo, delayed treatment, or no treatment
 KQs 1, 4, 5: Studies with an active comparator group

KQ 2: Screening interventions that do not include a reference standard
Outcomes KQs 1, 4:

Health Outcomes:

  • Preterm delivery (prior to 37 weeks’ gestation):
    • Spontaneous preterm delivery
    • Indicated preterm delivery
    • All-cause preterm delivery
  • Low birth weight
  • Preterm labor
  • Preterm premature rupture of membranes
  • Second-trimester fetal loss
  • Spontaneous abortion
  • Intrauterine fetal demise
  • Neonatal sepsis
  • Neonatal death

Intermediate Outcome:

  • Clearing of bacterial vaginosis after treatment

KQ 2: Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, normalized frequency (e.g., x of y tests are true positives or false positives)

KQ 3: Anxiety, distress

KQ 5:

  • Harms related to fetal exposure to medication:
    • Teratogenesis (e.g., congenital anomalies)
    • Carcinogenesis
  • Maternal adverse effects, such as:
    • Tolerability
    • Vaginal candidiasis
    • Serious adverse events (e.g., those resulting in the need for medical attention)
 KQs 1, 2, 4: Outcomes not specifically listed as included
Timing All KQs: Treatment provided after diagnosis

KQs 1, 3, 4, 5: Outcomes measured during current pregnancy at any point after screening or treatment, up to 30 days postdelivery; for harms of fetal exposure, outcomes measured at any time point

KQ 2: Screening test and reference standard assessed at same encounter

 KQs 1, 3, 4, 5: Outcomes not measured during current pregnancy or within 30 days of delivery, except for harms related to fetal exposure

KQ 2: Screening test and reference standard not assessed at same encounter
Setting
  • Any clinical care settings providing prenatal care, including general obstetrics practices, family medicine practices, and public health clinics
  • Studies conducted in countries categorized as “very high” on the Human Development Index (as defined by the United Nations Development Programme)
 Studies conducted in countries not categorized as “very high” on the Human Development Index
Study design KQs 1, 4: RCTs, controlled trials, or systematic reviews of RCTs or controlled trials that use study selection criteria similar to this review†

KQ 2: Diagnostic test accuracy studies or systematic reviews of diagnostic test accuracy that use study selection criteria similar to this review†

KQs 3, 5: RCTs, controlled trials, cohort studies, case-control studies, or systematic reviews that use study selection criteria similar to this review†

 Editorials, narrative reviews, letters to the editor, and study designs not listed as specifically included (e.g., case reports, case series, studies without a comparison group); publications not reporting original research
Language English language Languages other than English
Study quality Good- and fair-quality studies Poor-quality studies will be excluded from the main analyses but will be synthesized in sensitivity analyses if good- or fair-quality studies are not available

* Other diagnostic tests will be included if the following criteria are met: 1) test is feasible for use in primary care settings, 2) test is evaluated in a separate cohort from the one in which the test was initially developed and validated, and 3) test is evaluated with a priori defined test thresholds.
†  Only the most recent systematic review will be included if there are multiple reviews from the same group of investigators using the same review protocol. When there are several systematic reviews on the same topic and similar included primary studies, the review with the lowest risk of bias and the latest cutoff date for the literature search will be selected.

Abbreviation: RCT=randomized, controlled trial.

The draft Research Plan was posted on the USPSTF Web site for public comment from February 22 to March 21, 2018. One comment requested that the population of interest be expanded to include adolescents and women with abnormal vaginal flora and intermediate flora in addition to those with bacterial vaginosis. In response, the USPSTF added a Contextual Question to address this population. Some comments requested additional KQs for assessing the variation in benefits and harms of screening and treatment for additional subpopulations (e.g., persons with coexisting sexually transmitted infections, persons with Group B streptococcus colonization). The USPSTF added to the KQs to address the subpopulations for which some evidence may exist. Some comments requested changes in the terminology used to describe the included population or outcomes and clarification on included diagnostic tests and comparators; the USPSTF made revisions in response to these comments. In addition, the USPSTF removed persons living with HIV as an excluded population. Some comments requested the addition of secnidazole as an eligible treatment; the USPSTF did not include this drug because none of the existing drug trials enrolled pregnant adolescents and women. Lastly, some comments requested changes that would not be consistent with current USPSTF methods (e.g., including non-English–language studies, studies in developing countries, and cohort and case-control study designs for KQs on benefits of screening and treatment); thus, the USPSTF did not make any changes in response to these comments.