Objective To ascertain whether metronidazole treatment of women with a heavy growth of Gardnerella Design A multicentre, randomised, placebo-controlled trial Setting Four metropolitan hospitals.Participants Eight hundred and seventy-nine singleton women with a heavy growth of G. vaginalis or Interventions Oral metronidazole (400 mg) or placebo twice daily for two days at 24 weeks of gestation, Main outcome measures Spontaneous preterm birth less than 37 weeks.Results Intention-to-treat analysis showed no difference between metronidazole and placebo groups in overall preterm birth (3 1

Objective— To study the vaginal flora of women in preterm labour (PTL) and determine whether the presence of specific vaginal microflora is significantly associated with onset of PTL.Design— A comprehensive prospective study of the vaginal microflora of women in early labour comparing women in PTL with term controls. Microbiological assessment included cultures for aerobic and anaerobic bacteria, yeasts, genital mycoplasmas and Trichomonas vaginalis. Multiple logistic regression analysis was used to adjust for confounding obstetric and demographic variables.Setting— The Queen Victoria Hospital, Adelaide.Patients— 428 Women in PTL compared to 568 women in labour at term.Main outcome measure— PTL and preterm prelabour rupture of membranes (PPROM) in relation to specific vaginal microflora.Results— After multiple logistic regression analysis, two distinct bacteriological groupings were associated with PTL <37 weeks gestation, namely, the bacterial vaginosis group of organisms, Gardnerella vaginalis and Bacteroides spp., and a group of enteropharyngeal organisms, E. coli, Klebsiella spp., Haemophilus spp. and S. aureus. G. vaginalis was found in 12% of women in PTL compared to 6% at term [regression odds ratio (ROR) 1.8, 95% confidence intervals (CI) 1.1–3.1] whereas Bacteroides spp. were detected in 45% of women in PTL compared with 35% at term (ROR 1.6, CI 1.2–2.1). The prevalence of G. vaginalis (17%) and Bacteroides spp. (50%) was even higher in women in PTL <34 weeks gestation. The enteropharyngeal group of organisms were more commonly present in women in PTL <37 weeks (E. coli 10% vs 6%, ROR 1.4, CI 0.8–2.4; Klebsiella spp. 3% vs <1%, ROR 5.4, CI 1.1–26.7; Haemophilus spp. 2% vs <1%, ROR 5.5, CI 1.1–28.6; aureus 6% vs 4%, ROR 1.8, CI 0.9–3.3) and were isolated even more frequently in women in PTL <34 weeks (E. coli 15%; Klebsiella spp. 4%; S. aureus 7%). Bacteroides spp., Klebsiella spp., and Haemophilus spp. were all found to be associated with PPROM.Conclusion— There are two distinct bacteriological groupings commonly found in women in PTL, especially in PTL <34 weeks gestation. These bacteriological groups are women with bacterial vaginosis in pregnancy and women who demonstrate enteropharyngeal bacteria in the vagina.

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Subclinical genital tract infection has been clearly established as a significant cause of spontaneous preterm birth, particularly in early gestations. Bacterial vaginosis organisms rank highly among the pathogens involved in preterm labour and there is considerable beneficial evidence from the use of prophylactic antibiotics for women at high risk of preterm birth. The pathogenesis involves activation of macrophages and the generation of pro-inflammatory cytokines. Bronchopulmonary dysplasia is seen in the most immature of survivors and appears to be secondary to interruption of normal development and maturation of the lungs. The link between chorioamnionitis and lung injury in utero and subsequent development of bronchopulmonary dysplasia has now been substantiated. Exposure to pro-inflammatory cytokines is implicated in the impairment of the fetal lung. A significant body of evidence supports the association between chorioamnionitis, periventricular leukomalacia and cerebral palsy. Biological mechanisms that explain the association between chorioamnionitis and fetal brain injury involve pro-inflammatory cytokines. Similarity in the pattern of expression of cytokines suggests a common pathway for the initiation of preterm labour and also injury to the lung and the central nervous system of the fetus.

A prospective study of the vaginal flora changes between midtrimester and labor was undertaken in 560 women; 337 had intact membranes and were in labor when swabs were taken. Of these, 45 delivered preterm. Gardnerella vaginalis, Ureaplasma urealyticum (both associated with preterm birth when present in midtrimester), and Mycoplasma hominis commonly persisted between midtrimester and labor, particularly in the preterm cohort (24 [65%] of 37 midtrimester isolates), and these organisms were seldom acquired late in pregnancy. A second group, Bacteroides species, had both a high persistence (9 [60%] of 15 midtrimester isolates) and high late acquisition rate (10 [53%] of 19 labor isolates) in the preterm cohort. These findings provide a rationale for treatment of bacterial vaginosis in pregnancy. A third group, comprising enteropharyngeal bacteria and Peptostreptococcus species, were almost all acquired late in the preterm cohort (14 [88%] of 16 labor isolates), and persistence from midtrimester was rare.