A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. Antimicrobial prophylaxis in pregnancy: a randomized, placebo-controlled trial with cefetamet-pivoxil in pregnant women with a poor obstetric history. Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. Mass antimicrobial treatment in pregnancy. A randomized, placebo-controlled trial in a population with high rates of sexually transmitted diseases. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial. Erythromycin treatment of pregnant women to reduce the incidence of low birth weight and preterm deliveries.
To determine whether metronidazole reduces early preterm labour in asymptomatic women with positive vaginal fetal fibronectin (fFN) in the second trimester of pregnancy.
                Randomised placebo-controlled trial.
                Fourteen UK hospitals (three teaching).
                Pregnancies with at least one previous risk factor, including mid-trimester loss or preterm delivery, uterine abnormality, cervical surgery or cerclage.
                Nine hundred pregnancies were screened for fFN at 24 and 27 weeks of gestation. Positive cases were randomised to a week's course of oral metronidazole or placebo.
                Primary outcome was delivery before 30 weeks of gestation. Secondary outcomes included delivery before 37 weeks.
                The Trial Steering Committee (TSC) recommended the study be stopped early; 21% of women receiving metronidazole (11/53) delivered before 30 weeks compared with 11% (5/46) taking placebo [risk ratio 1.9, 95% confidence interval (CI) 0.72-5.09, P = 0.18]. There were significantly more preterm deliveries (before 37 weeks) in women treated with metronidazole 33/53 (62%) versus placebo 18/46 (39%), risk ratio 1.6, 95% CI 1.05-2.4. fFN was a good predictor of early preterm birth in these asymptomatic women; positive and negative predictive values (24 weeks of gestation) for delivery by 30 weeks were 26% and 99%, respectively (positive and negative likelihood ratios 15, 0.35).
                Metronidazole does not reduce early preterm birth in high risk pregnant women selected by history and a positive vaginal fFN test. Preterm delivery may be increased by metronidazole therapy. This study was undertaken to measure the impact of a single oral dose of cefetamet-pivoxil on pregnancy outcome in a population with substantial rates of low birth weight and high prevalence rates of maternal infections.
                A total of 320 pregnant women with a poor obstetric history, defined as a history of low birth weight or stillbirth, were randomized to receive a single oral dose of 2 gm of cefetamet-pivoxil or a placebo at a gestational age between 28 and 32 weeks. Patients were assessed at delivery and 1 week post partum for pregnancy outcome, postpartum endometritis, human immunodeficiency virus-1 and gonococcal infections.
                A total of 253 (79%) women gave birth at the maternity hospital, of whom 210 (83%) attended the follow-up clinic. Overall, 18.1% of these pregnant women were human immunodeficiency virus-1 seropositive, whereas 9.5% had antibodies against Treponema pallidum. There was a significant difference between cefetamet-pivoxil- and placebo-treated women in infant birth weight (2927 gm vs 2772 gm, p = 0.03) and low birth weight (< 2500 gm) rates (18.7% vs 32.8%, p = 0.01, odds ratio 2.1, 95% confidence interval 1.2 to 3.8). The stillbirth rate was 2.2% in the cefetamet-pivoxil group and 4.2% in the placebo group (not significant). Postpartum endometritis was found in 17.3% in the intervention arm versus 31.6% in the placebo group (p = 0.03, odds ratio 2.2, 95% confidence interval 1.1 to 7.6). Neisseria gonorrhoeae was isolated from the cervix in 5 of 103 (4.9%) women in the intervention and in 14 of 101 (13.9%) in the placebo group (p = 0.04, odds ratio 3.2, 95% confidence interval 1.1 to 10.5).
                A single oral dose of cefetamet-pivoxil administered to pregnant women with a poor obstetric history seemed to improve pregnancy outcome in this population with high rates of maternal infections. Larger studies should be carried out to examine the public health impact, the feasibility, and the overall cost/benefit ratio of this intervention. Available information suggests that some instances of preterm birth or premature rupture of membranes are associated with clinically unrecognized infection and inflammation of the lower uterine segment, decidua, and fetal membranes. Various cervicovaginal microorganisms have been recovered from these sites. Many of these microorganisms produce factors that may lead to weakening of the fetal membranes, release of prostaglandins, or both. This study evaluated the presence of various lower genital tract microflora and bacterial conditions in 229 women enrolled in a double-blind, placebo-controlled trial of short-course erythromycin treatment at 26 to 30 weeks' gestation to prevent preterm birth. Demographic, obstetric, and microbiologic parameters were prospectively evaluated. Premature rupture of membranes occurred less frequently (p less than 0.01) among women who received erythromycin (6%) versus placebo (16%). Preterm premature rupture of membranes also occurred less frequently, although not significantly (p = 0.3) in patients who received erythromycin (2%) versus placebo (5%). Erythromycin treatment significantly decreased the occurrence of premature rupture of membranes among women who were initially positive for Chlamydia trachomatis infection. Logistic regression analysis demonstrated that C. trachomatis (p = 0.05; odds ratio, 9), vaginal wash phospholipase C (p = 0.08; odds ratio, 6) and prior preterm birth (p = 0.007; odds ratio 17) were associated with increased risk of preterm birth. Bacterial vaginosis, Mycoplasma hominis, Ureaplasma urealyticum were not significantly associated with increased risk of preterm birth or preterm rupture of membranes. These findings support a role for selected lower genital tract microflora in preterm birth and premature rupture. Large controlled treatment trials of specific infections or conditions associated with preterm birth and premature rupture of membranes are required to confirm the value of antimicrobial treatments in prevention of microbial-associated preterm birth. Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery. We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks' gestation.
                In 624 pregnant women at risk for delivering prematurely, vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks' gestation. We then performed a 2:1 double-blind randomization to treatment with metronidazole and erythromycin (433 women) or placebo (191 women). After treatment, the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time (a mean of 27.6 weeks' gestation).
                A total of 178 women (29 percent) delivered infants at less than 37 weeks' gestation. Eight women were lost to follow-up. In the remaining population, 110 of the 426 women assigned to metronidazole and erythromycin (26 percent) delivered prematurely, as compared with 68 of the 190 assigned to placebo (36 percent, P = 0.01). However, the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis (rate of preterm delivery, 31 percent with treatment vs. 49 percent with placebo; P = 0.006). Of the 358 women who did not have bacterial vaginosis when initially examined, 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely (P = 0.55). The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery (preterm delivery in the treatment group, 39 percent; and in the placebo group, 57 percent; P = 0.02) and in women who weighed less than 50 kg before pregnancy (preterm delivery in the treatment group, 14 percent; and in the placebo group, 33 percent; P = 0.04).
                Treatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery. Sexually transmitted diseases (STDs) are highly prevalent in pregnant women in many developing countries and have been associated with poor obstetric outcomes. Case detection and treatment of STDs in women is problematic and expensive, underscoring the need for other strategies. To explore the potential benefits of routine antimicrobial therapy on pregnancy outcome, we carried out a randomized, double-blind, clinical trial in one of the antenatal clinics in Nairobi, Kenya. Four hundred pregnant women between 28 and 32 weeks' gestation were given a single dose of 250 mg ceftriaxone intramuscularly or a placebo. There was a significant difference between ceftriaxone and placebo-treated women in infant birth weight (3,209 versus 3,056 g, P = .01). In addition, there was a trend toward lower rates of birth weight < 2,500 g (4.0% versus 9.2%, P = .08) and postpartum endometritis (3.8% versus 10.4%, P = .05) in the intervention than in the placebo group. Neisseria gonorrhoeae was isolated from the cervixes of postpartum women in 1.8% of the intervention group as compared to 4.2% of the control group. These data suggest a beneficial effect of antimicrobial prophylaxis on pregnancy outcome. Larger studies should be carried out to examine the public health impact of this intervention. To test the hypothesis that prophylactic administration of clindamycin 2% vaginal cream can reduce the incidence of preterm birth in a high risk population.
                A multi-centre, randomised, double-blind, placebo-controlled trial.
                Twelve city hospitals in The Netherlands.
                One hundred and sixty-eight women with a singleton pregnancy and a history of a spontaneous preterm delivery in the preceding pregnancy.
                Clindamycin 2% vaginal cream, or placebo cream, administered daily for seven days at 26 and 32 weeks of gestation.
                Spontaneous preterm birth at < 37 weeks, admission for threatened preterm labour, neonatal infectious morbidity.
                In the intention-to-treat analysis no difference was found in overall preterm birth between clindamycin and placebo (23% vs 18%, respectively). In the subgroup who completed the trial and administered all medication, more women delivered before 34 weeks in the clindamycin group (1.4% in the placebo vs 9.0% in the clindamycin group; P < 0.05). The length of admissions for threatened preterm labour did not differ. More infectious neonatal morbidity was seen in the clindamycin group (5/83 vs 0/85; P < 0.05).
                Clindamycin 2% vaginal cream given prophylactically to women with a spontaneous preterm birth in the preceding pregnancy did not prevent preterm delivery or reduce the number of admissions for threatened preterm labour. The neonatal infectious morbidity in the group treated with clindamycin was significantly higher and a major concern. nan
Antibiotic prophylaxis given during the second or third trimester of pregnancy reduces the risk of prelabour rupture of membranes and postpartum endometritis when given routinely to pregnant women. However there was also a possible substantial bias in the review's results because of a high rate of loss to follow up and small numbers of studies for each of our analyses. So we conclude that there is not enough evidence to recommend the use of routine antibiotics during pregnancy to prevent infectious adverse effect on pregnancy outcomes.