Bacterial Vaginosis and Pregnancy: Clinical Overview and Public Health Implications

1
Bacterial Vaginosis and Pregnancy Clinical
Overview and Public Health Implications

• Deborah B. Nelson, Ph.D.
• Assistant Professor
• Center for Clinical Epidemiology and
  Biostatistics
• University of Pennsylvania School of Medicine

http//www.med.upenn.edu/crrwh/Nelson.html
2
Learning Objectives

• Review the Prevalence, Identification, and
  Treatment of Bacterial Vaginosis (BV)
• Describe the Epidemiology and Consequences of
  Bacterial Vaginosis in Pregnancy
• Discuss Current Research Findings
• Present the BEAR Project Hypothesis, Specific
  Aims and Methodology

Nelson DB, Macones GA. Bacterial Vaginosis in
Pregnancy Current Findings and Future
Directions. Epidemiologic Reviews 2002 (24
102-108).
3
Bacterial Vaginosis Clinical Background

• BV is the most frequent cause of vaginal
  discharge
• 3 million cases of BV 800,000 cases among
  pregnant women annually (Goldman Hatch 2000).
• Prevalence of BV 25-60 among nonpregnant
  women 10-35 among pregnant women (Goldman
  Hatch 2000).

4
Bacterial Vaginosis Microbiology

• The normal vagina is an acidic environment
  inhabited primarily by hydrogen-producing
  lactobacilli
• There is some change in the microbiological flora
  of the vagina (due to environmental, behavioral,
  or hormonal factors)
• BV is characterized by a reduced number of
  lactobacilli and an overgrowth of gram negative,
  anaerobic bacteria.

5
Bacterial Vaginosis Microbiology

• Anaerobic organisms in BV include Mycoplasma
  hominis, Bacteroides spp., Mobiluncus spp.,
  Gardnerella vaginalis.
• Increase in polyamines resulting in the
  characteristic odor of BV and the increase in
  epithelial cell exfoliation.

6
Bacterial Vaginosis Clinical Diagnosis

• Amsel criteria
• three of four clincal conditions
• An elevated vaginal pH (gt 4.5).
• Amine odor with KOH (whiff test).
• Presence of clue cells (20 of cells).
• Homogeneous vaginal discharge.

7
Bacterial Vaginosis Amsels Clinical Diagnosis

• At least 20 clue cells on wet mount.
• However, gardnerella present 16-42 women without
  BV.

8
Bacterial Vaginosis Amsels Clinical Diagnosis

• Assessment of vaginal pH lacks specificity
• Conduct of Whiff test is subjective and lacks
  sensitivity
• Identification of clue cells subjected to skill
  and interpretation of the microscopist

9
Bacterial Vaginosis Nugents Clinical Diagnosis

• Gram stain using Nugents criteria
• High sensitivity and specificity
• Permanent record
• Commonly used in epidemiologic studies (NICHD
  maternal-fetal medicine unit)

10
Bacterial Vaginosis Clinical Diagnosis

• Gram stain using Nugents criteria

Gardnerella/ Bacteroides
Lactobacillus
Mobiluncus
Total score gt 7 indicates BV, 4-6 intermediate
stage of BV
11
Bacterial Vaginosis Treatment

• Oral Treatment
• Metronidazole (Flagyl)
• Clindamycin (Cleocin)
• Topical Treatment
• Metronidazole 0.75 vaginal cream (Metrogel)
• Clindamycin 2 vaginal cream

12
Bacterial Vaginosis in Pregnancy Epidemiology

• Race
• Socioeconomic status
• Sexual activity
• Vaginal douching
• Drug use
• Psychosocial stress

13
Bacterial Vaginosis Clinical Implications

• Pelvic Inflammatory Disease
• Post-hysterectomy vaginal cuff cellulitis
• Plasma cell endometritis

14
Bacterial Vaginosis and Pregnancy Clinical
Implications

• Amniotic fluid infection
• Postpartum endometritis
• Preterm delivery
• Preterm labor
• Premature rupture of the membranes
• Spontaneous abortion (?)

15
Bacterial Vaginosis and Pregnancy Current
Research
Preterm Delivery

• Hillier et al, 1995
• 10,000 pregnant women
• 16 BV RR 1.4 (95 CI 1.1-1.8).
• Gratacos et al, 1998
• 635 pregnant women
• 20 BV RR 3.1 (95 CI 1.8-29.4).

• Kurki et al, 1992
• 790 pregnant women
• 21 BV RR 6.9 (95 CI 2.5-18.8).

16
Bacterial Vaginosis Treatment paradigm in a
pregnant population

• Pregnant women

Symptomatic
Asymptomatic
High risk
Low risk
Screen
Screen
Screen (?)
Treatment
No Treatment
Treatment (?)
No treatment
(Hauth 1995, Morale 1994, McDonald 1997, Carey
2001)
17
Bacterial Vaginosis and PTD Current Research

• Preterm Prediction Study (Goepfert et al, 2001)
  BV, cervical interleukin-6 concentration, fetal
  fibronectin level, short cervical length.
• Indicators of PTL (Hitti, Hillier et al, 2001)
  Interleukin-6 and -8, neutrophils, BV and other
  predictors of amniotic fluid infection.

18
Bacterial Vaginosis and Spontaneous Abortion
Current Research

• Sub-analyses
• RR 5.5 (95 CI 2.3 - 13.3) Hay et al, 1994
• RR 3.2 (95 CI 1.4 - 6.9) McGregor et al 1995
• High risk populations
• RR 2.67 (95 CI 1.26 - 5.63) Ralph et al 1999

19
Spontaneous Abortion Epidemiology
Maternal age
Previous spontaneous abortion
Prenatal cigarette smoking
Prenatal cocaine use
Chromosomal anomalies
20
Bacterial vaginosis Evaluation And early
Reproduction
BEAR Project
21
BEAR Project Study Design

• Four year NICHD-funded study.
• Prospective cohort enrolling women seeking
  prenatal care.
• Exposure Bacterial Vaginosis.
• Outcome Spontaneous Abortion.
• 30 month data collection period (N2200).

22
BEAR Project Specific Aims

• Aim 1 Among women seeking prenatal care at urban
  obstetric clinics, characterize the prevalence
  and predictors of BV.
• Aim 2 Evaluate whether BV during pregnancy is an
  important, independent predictor of SAB.

23
BEAR ProjectEligibility Criteria

• OB patient at their first prenatal care visit
  seen at the Gates clinic or PTP.
• 12.6 weeks gestation or earlier based on last
  menstrual period.
• Resident of Philadelphia.
• Single, intrauterine pregnancy.

24
BEAR Project Study Methods

• Baseline data collection (Nurse Coordinators)
• Enroll women and obtain informed consent.
• Collect vaginal swabs for all eligible women
  (regardless of symptoms).
• Obtain urine sample.
• Administer 15 minute questionnaire.

25
BEAR ProjectBaseline Questionnaire

• Risk factors for BV race, prior and current
  sexual activity, douching, drug use, psychosocial
  stress measures.
• Risk factors for SAB age, prior pregnancy
  information, drug use, vaginal bleeding.

26
BEAR Project Study Methods

• Follow-up data collection (Follow-up Coordinator)
• Conduct follow-up telephone interviews.
• Medical confirmation of outcomes through medical
  record review.
• Classify women as eligible and either a case or
  pregnant control.

27
BEAR ProjectFollow-up Questionnaire

• Determine pregnancy status at 20 weeks gestation.
• Identify subsequent diagnoses of BV and
  compliance with medical therapy.
• Measure other risk factors for SAB.

28
BEAR Project Study Methods

• Control Pregnant women maintaining their
  pregnancy through 20 weeks gestation.

• Case Women experiencing a spontaneous abortion
  during the study period (20 weeks).

29
BEAR Project Goals

• Determine the prevalence of symptomatic and
  asymptomatic BV among women in first trimester of
  pregnancy.
• Identify predictors of BV in the first trimester
  (ie. stress, douching, prior pregnancy outcomes).

30
BEAR Project Goals

• Examine the independent relationship between BV
  and spontaneous abortion.
• Assess the separate relationship between
  symptomatic and asymptomatic BV and spontaneous
  abortion.

31
Bacterial Vaginosis and Pregnancy Clinical
Implications and Current Research

• Deborah B. Nelson, Ph.D.
• Assistant Professor
• Center for Clinical Epidemiology and
  Biostatistics
• University of Pennsylvania School of Medicine