A Cochrane review [Abstract] 1 included 21 good quality trials with a total of 7 847 women (oral metronidazole: 5 trials; oral metronidazole plus erythromycin, oral clindamycin, ampicillin, vaginal metronidazole gel, 1 trial each; intravaginal clindamycin alone: 6 trials). Ten trials performed microbiological follow up and seven trials gave a second course of treatment (four only if bacterial vaginosis (BV) was not eradicated). Antibiotic therapy was effective at eradicating bacterial vaginosis during pregnancy (RR 0.42; 95% CI 0.31 to 0.56; 10 trials, n=4403, I² = 91%). Antibiotic treatment also reduced the risk of late miscarriage (RR 0.20; 95% CI 0.05 to 0.76; 2 trials, n=1270, I² = 0%). Treatment did not reduce the risk of preterm birth (PTB) before 37 weeks (average RR 0.88; 95% CI 0.71 to 1.09; 13 trials, n=6491, I² = 48%), or the risk of preterm prelabour rupture of membranes), or the risk of preterm prelabour rupture of membranes (PPROM) (RR 0.74; 95% CI 0.30 to 1.84; 2 trials, n=493 women). Treatment before 20 weeks' gestation did not reduce the risk of preterm birth less than 37 weeks (average RR 0.85; 95% CI 0.62 to 1.17; 5 trials, n=4088 women, I² = 49%). In women with a previous PTB, treatment did not affect the risk of subsequent PTB (average RR 0.78; 95% CI 0.42 to 1.48; 3 trials, n=421, I² = 72%).However, in women with abnormal vaginal flora (intermediate flora or bacterial vaginosis) treatment may reduce the risk of PTB before 37 weeks (Peto OR 0.51, 95% CI 0.32 to 0.81; 2 trials, 894 women). There was no difference between oral antibiotics versus vaginal antibiotics for the risk of PTB.
Another Cochrane review 2 (abstract , review [Abstract]) included one trial of antibiotic treatment for vaginal ureaplasma in pregnancy. 644 women received antibiotic treatment (erythromycin estolate, erythromycin stearate, clindamycin hydrochloride) and 427 received placebo. The incidence of low birthweight (< 2500 grams) was only evaluated for erythromycin (n=398) compared to placebo (n=427) and the difference was nonsignificant (RR 0.70, 95% CI 0.46-1.07). Data on preterm birth was not reported.
A multicentre, double-blind RCT 4 assessed whether treatment of bacterial vaginosis decreases late miscarriages or spontaneous very preterm birth. 84 530 pregnant women before 14 weeks' gestation were screened. 5630 had BV, of whom 3105 were randomly assigned to groups in the low-risk trial (n=943 to receive single-course clindamycin, n=968 to receive triple-course clindamycin, and n=958 to receive placebo) or high-risk subtrial (n=122 to receive single-course clindamycin and n=114 to receive triple-course clindamycin). In 2869 low-risk pregnancies, the primary outcome occurred in 22 (1.2%) of 1904 participants receiving clindamycin and 10 (1.0%) of 956 participants receiving placebo (RR 1.10, 95% CI 0.53 to 2.32; p=0.82). In 236 high-risk pregnancies, the primary outcome occurred in 5 (4.4%) participants in the triple-course clindamycin group and 8 (6.0%) participants in the single-course clindamycin group (RR 0.67, 95% CI 0.23 to 2.00; p=0.47). In the low-risk trial, adverse events were more common in the clindamycin groups than in the placebo group (58 [3.0%] of 1904 vs 12 [1.3%] of 956; p=0.0035). The most commonly reported adverse event was diarrhoea (30 [1.6%] in the clindamycin groups vs 4 [0.4%] in the placebo group; p=0.0071). No severe adverse event was reported in any group. Adverse fetal and neonatal outcomes did not differ significantly between groups in the high-risk subtrial.
A retrospective study 3 analyzed the relationship between the vaginal bacterial status and the preterm delivery rate. Without treatment, the preterm delivery rate was higher in the BV subgroup than in the I and normal (N) subgroups (p = 0.021) in the early gestational period, whereas the rates in the BV and I subgroups were higher than in the N subgroup in the middle gestational period (p = 0.0003). Although treatment of BV by metronidazole vaginal tablets significantly increased the N subgroup in the middle gestational period (p = 0.020), there was no significant improvement in the preterm delivery rate.
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