General obstetrics: A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study

Abstract

Objective To determine whether metronidazole reduces early preterm labour in asymptomatic women with positive vaginal fetal fibronectin (fFN) in the second trimester of pregnancy.Design Randomised placebo-controlled trial.Setting Fourteen UK hospitals (three teaching).Population Pregnacies with at least one previous risk factor, including mid-trimester loss or preterm delivery, uterine abnormality, cervical surgery or cerclage.Methods 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.Main outcome measures Primary outcome was delivery before 30 weeks of gestation. Secondary outcomes included delivery before 37 weeks.Results 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).Conclusion 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.Please cite this paper as: Shennan A, Crawshaw S, Briley A, Hawken J, Seed P, Jones G, Poston L. A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG 2006; 113:65-74.

Practices for predicting and preventing preterm birth in Ireland: a national survey

“…Despite this, 17% of respondents do not routinely prescribe antibiotics for women symptomatic for preterm birth. Of those who do prescribe antibiotics for PPROM, erythromycin is the most commonly prescribed antibiotic and this is reflective of best practice recommendations [28][29][30][31]. The findings from this survey reflect the conflicting evidence on the routine use of cervical cerclage for preventing preterm birth [32][33][34], with 13% of consultant obstetricians routinely inserting an elective cervical cerclage in women with a history of one or more mid-trimester miscarriages (15-22 weeks gestation), whilst 70% would consider inserting an emergency cervical cerclage.…”

Prophylactic antibiotics for the prevention of preterm birth in women at risk: A meta‐analysis

“…Metronidazole alone was used in six studies. 8,9,11,16,19,23 Only one individual study showed a significant advantage to metronidazole use in reducing PTB prior to 37 weeks gestation. 23 Two individual studies showed no significant effect; 9,16 whereas the remaining three all showed a significant adverse effect on preterm delivery with metronidazole use.…”

“…10,18 For the three studies that principally assessed risk based on previous preterm delivery (with or without abnormal vaginal flora), one used metronidazole, 23 one used clindamycin 22 and one used a combination of metronidazole and erythromycin. 24 For the two studies assessing risk based on positive fetal fibronectin, one used metronidazole, 8 and the other a combination of metronidazole and erythromycin. 21 The studies in this review followed a randomised double-blind, placebo-controlled standard.…”

“…9-20 Two focussed on antibiotic therapy for women deemed at risk from their fibronectin status. 8,21 Three gave antibiotics for those with previous preterm deliveries (one recruiting women with previous preterm deliveries, a second recruiting women with previous preterm deliveries and BV, and a third recruiting women with previous preterm delivery with and without BV). [22][23][24] For those evaluating the effect of abnormal vaginal flora, four used metronidazole, 9,11,16,19 six used clindamycin [12][13][14][15]17,20 and two used erythromycin.…”

Pregnancy and Breastfeeding in Patients with Crohn’s Disease

“…However, a randomized controlled trial of 7 days of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin (the PREMET Study) showed that in this selected non-IBD population, preterm delivery (<37 weeks) was increased by metronidazole therapy (33/53 vs. 18/46 for placebo, CI 1.05–2.4) [30]. Loebstein et al [31] prospectively enrolled and followed up 200 women exposed to fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin) during gestation.…”