Bacterial Vaginosis and Pregnancy: Clinical Overview and

Public Health Implications

Deborah B. Nelson, Ph.D.Assistant Professor

Center for Clinical Epidemiology and BiostatisticsUniversity of Pennsylvania School of Medicine

http://www.med.upenn.edu/crrwh/Nelson.html

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).

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).

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.

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.

Bacterial Vaginosis: Clinical Diagnosis

1. Amsel criteria: three of four clincal conditions

• An elevated vaginal pH (> 4.5).• Amine odor with KOH (whiff test).• Presence of clue cells (20% of cells).• Homogeneous vaginal discharge.

Bacterial Vaginosis: Amsel’s Clinical Diagnosis

• At least 20% clue cells on wet mount.

• However, gardnerella present 16-42% women without BV.

Bacterial Vaginosis: Amsel’s 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

Bacterial Vaginosis: Nugent’s Clinical Diagnosis

Gram stain using Nugent’s criteria:

• High sensitivity and specificity • Permanent record• Commonly used in epidemiologic

studies (NICHD maternal-fetal medicine unit)

Bacterial Vaginosis: Clinical Diagnosis

Gram stain using Nugents criteria:

Qty Score Qty Score Qty Score

4+ 0 0 0 0 0 3+ 1 1+ 1 1+ or 2+ 1

2+ 2 2+ 2 3+ or 4+ 2

1+ 3 3+ 3

0 4 4+ 4

LactobacillusGardnerella/Bacteroides Mobiluncus

Total score: >= 7 indicates BV, 4-6 intermediate stage of BV

Bacterial Vaginosis: Treatment

• Oral Treatment–Metronidazole (Flagyl)

–Clindamycin (Cleocin)

• Topical Treatment–Metronidazole 0.75% vaginal cream

(Metrogel)

–Clindamycin 2% vaginal cream

Bacterial Vaginosis in Pregnancy:

EpidemiologyRace

Socioeconomic status

Sexual activity

Vaginal douching

Drug use

Psychosocial stress

Bacterial Vaginosis: Clinical Implications

• Pelvic Inflammatory Disease

• Post-hysterectomy vaginal cuff cellulitis

• Plasma cell endometritis

Bacterial Vaginosis and Pregnancy:

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

Bacterial Vaginosis and Pregnancy:

Current Research

–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).

Preterm Delivery

Bacterial Vaginosis: Treatment paradigm in a pregnant

populationPregnant women

Symptomatic Asymptomatic

High risk Low risk

Screen

Treatment (?) No treatment

Screen (?)

(Hauth 1995, Morale 1994, McDonald 1997, Carey 2001)

Treatment No Treatment

Screen

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.

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

Spontaneous Abortion Epidemiology

Maternal age

Previous spontaneous abortionPrenatal cigarette smoking

Prenatal cocaine use

Chromosomal anomalies

Bacterial vaginosis Evaluation And early Reproduction

BEAR Project:

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 (N=2200).

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.

BEAR Project:Eligibility 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.

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.

BEAR Project:Baseline

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.

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.

BEAR Project:Follow-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.

BEAR Project: Study Methods

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

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

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).

BEAR Project: Goals

• Examine the independent relationship between BV and spontaneous abortion.

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

Bacterial Vaginosis and Pregnancy: Clinical Implications and

Current Research

Deborah B. Nelson, Ph.D.Assistant Professor

Center for Clinical Epidemiology and BiostatisticsUniversity of Pennsylvania School of Medicine