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Vaginal Infections and Preterm Birth - An Update

Overview. HistoryRationaleAsymptomatic bacteriuriaGonorrheaSyphilisGenital Mycoplasmas. Chlamydia trachomatisGroup B strepPeriodontal diseaseBacterial vaginosisTrichomonas vaginalis. Rationale. Preterm birth is the leading cause of neonatal morbidity and mortalityIncreasing body of eviden

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Vaginal Infections and Preterm Birth - An Update

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    1. Vaginal Infections and Preterm Birth - An Update J. Chris Carey, MD

    2. Overview History Rationale Asymptomatic bacteriuria Gonorrhea Syphilis Genital Mycoplasmas Chlamydia trachomatis Group B strep Periodontal disease Bacterial vaginosis Trichomonas vaginalis

    3. Rationale Preterm birth is the leading cause of neonatal morbidity and mortality Increasing body of evidence to indicate that infections are associated with preterm birth

    4. Evidence linking infection with preterm birth Histologic Chorioamnionitis is more common in preterm deliveries Postpartum endomyometritis is more common after preterm deliveries Preterm delivery is more common in women with a variety of genital infections

    5. % PPE by Gestational Age VIP study

    6. Risk factors for PPE

    7. Mechanism for preterm labor

    8. Asymptomatic bacteriuria Occurs in 3 - 10 % of pregnant women First asymptomatic infection to be linked to preterm birth

    9. Asymptomatic bacteriurea Kass (NY State J Med 1962:62: 2815) showed 24% preterm birth in untreated 10% in treated 10% in controls

    10. Asymptomatic bacteriurea Elder, AJOG 1971:111;441

    11. Asymptomatic bacteriurea Screen all women at first visit Treatment reduces risk of pyelonephritis

    12. Syphilis Effects of untreated syphilis include stillbirth, preterm birth and congenital anomalies Half of congenital syphilis occurs in women with no prenatal care Screen all pregnant women at first visit – high risk in third trimester

    13. Gonorrhea Occurs in 1 - 6 % of pregnant women Untreated gonorrhea associated with preterm delivery and PPROM Treatment of gonorrhea reduces risk

    14. Genital Mycoplasmas Ureaplasma urealyticum Found in 50 - 90% of pregnant women Early studies indicated strong association with preterm birth Later studies fail to confirm association

    15. Ureaplasma treatment trial - VIP 1181 women - 605 erythromycin, 576 placebo No difference in mean birth weight low birth weight delivery < 37 weeks delivery < 32 weeks

    16. Genital Mycoplasmas Mycoplasma hominis Inconclusive results from studies ? association with BV

    17. Chlamydia trachomatis Early studies showed a strong association with preterm delivery and neonatal death Later studies show an association with preterm delivery and low birth weight Treatment trials are inconclusive

    18. Chlamydia treatment trial - VIP

    19. Group B strep Early studies showed association between early onset GBS sepsis and preterm birth Early studies also showed association between preterm birth and GBS carriage Large study showed weak association Treatment trials showed no effect of therapy

    20. Group B Strep VIP study results GBS recovered from 21 % of 13,646 women Heavy colonization was associated with a modest risk of preterm low birth weight infant (RR 1.5, 95% CI 1.1-1.9 ) Light colonization showed no increase risk Treatment with antibiotics active against GBS reduced risk in heavily colonized women Regan et al AJOG 1996;174:1354-60

    21. Group B Strep treatment trial - VIP

    22. Group B Strep VIP study Randomized clinical trial of erythromycin did not reduce the risk of preterm birth in women colonized with GBS

    23. Bacterial vaginosis Occurs in 20 – 30 % of asymptomatic women Approximately 1,000,000 cases/yr in USA in pregnant women Numerous studies show association with preterm birth

    24. Bacterial vaginosis Gravett, 1986 JAMA N=534 pregnant women (102 with BV) BV associated with PROM (RR= 2.4) Preterm labor (RR = 2.0) IAI (RR = 2.7)

    25. Bacterial vaginosis Kurki - Obstet Gynecol 1992 N = 790 pregnant women BV by culture 21.4% BV by Gram stain 21.1% BV associated with PTL RR 2.6 PTB RR 6.9 PPROM RR 7.3

    26. Bacterial Vaginosis Hay – BMJ 1994 N=783, screened at 9-24 weeks BV associated with PTD – RR 2.8 Late miscarriage – 5.5

    27. Bacterial vaginosis Total of 11 studies show increase in PTB with RR ranging from 2 - 4

    28. Bacterial vaginosis VIP data – Hillier NEJM 1995 N = 10,397 women without chlamydia, TV or GBS BV in 1645 PTD – rr 1.4 LBW – rr 1.5

    29. BV treatment trials Clindamycin trials McGregor AJOG 1994 Joesoef AJOG 1995 Metronidazole trials Morales AJOG 1994 McDonald et al - Br J Obstet Gyn 1997;104:1391

    30. BV treatment trial Morales AJOG 1994

    31. Treatment of BV Hauth NEJM 1995 263 high-risk women with BV Randomized 2:1 metro + erythro or placebo Incidence of PTD < 37 w - 37% v 23% < 34 w - 19% v 11% < 32 w - 11% v 6%

    32. Treatment of BV McGregor AJOG 1994

    33. Treatment of BV Joeseof, AJOG 1995

    34. Other clindamycin trials

    35. McDonald BV trial 879 women with BV by Gram stain or culture for G Vaginalis at 19 weeks Oral metronidazole 400 mg BID for 2 days or placebo at 24 weeks and at 29 weeks if persistent

    36. McDonald BV trial

    37. Mc Donald BV trial

    38. MFMU BV Study NEJM 2000 Purpose – To determine whether treatment of BV with metronidazole would prevent preterm birth Screened from 8-22 weeks Treated with 2 grams metro on day 1 and 3 from 13 – 24 weeks Treatment repeated late second trimester

    39. MFMU BV study

    40. MFMU Trichomonas trial Carriage of T. vaginalis increases risk of preterm birth T. vaginalis commonly found with BV T. vaginalis is common and often asymptomatic

    41. Purpose To determine if metronidazole treatment would prevent preterm birth in asymptomatic women who carried T. vaginalis

    42. Results

    43. Results

    44. Randomized 297 patients randomized to placebo 320 randomized to metronidazole The study was stopped early by the Data Safety Monitoring Board

    45. Effectiveness of therapy

    46. Results

    47. Results

    48. What can we learn from the treatment trials of BV? Treatment of women with a prior PTD with metronidazole and erythromycin may reduce the risk of subsequent PTD but does not reduce the risk in women who do not have BV Women with a prior PTD may be in some way different

    49. What should we do in clinical practice? Screen and treat for gonorrhea, syphilis, asymptomatic bacteriuria, chlamydia Screen women with a prior PTD for BV and treat with metronidazole and erythromycin? DO NOT treat BV with clindamycin vaginal cream DO NOT treat asymptomatic trich

    50. Conclusions The more we learn, the less we know about infections and preterm delivery Antibiotic therapy in pregnancy may be harmful Treatment of infections in pregnancy should only be done if clear benefit has been shown from randomized trials

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