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 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.

7. Bacterial Vaginosis: Amsel’s Clinical Diagnosis At least 20% clue cells on wet mount. However, gardnerella present 16-42% women without BV.

8. 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

9. 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)

10. Bacterial Vaginosis: Clinical Diagnosis Gram stain using Nugents criteria: Lactobacillus Gardnerella/ Bacteroides Mobiluncus Total score: >= 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 – 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

16. Bacterial Vaginosis: Treatment paradigm in a pregnant population Pregnant women Symptomatic Asymptomatic High risk Low risk Screen Treatment (?)No treatment Screen (?) (Hauth 1995, Morale 1994, McDonald 1997, Carey 2001) TreatmentNo Treatment Screen

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 (N=2200).

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 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.

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 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.

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 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.

28. 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.

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