A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study.
OBJECTIVE
To determine whether metronidazole reduces early preterm labour in asymptomatic women with positive vaginal fetal fibronectin (fFN) in the second trimester of pregnancy.


METHODS
Randomised placebo-controlled trial.


METHODS
Fourteen UK hospitals (three teaching).


METHODS
Pregnancies 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.


METHODS
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).


CONCLUSIONS
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.
Shennan
Andrew
A
Maternal and Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development, St Thomas' Hospital, King's College London, UK.
Crawshaw
Sarah
S
Briley
Annette
A
Hawken
Jenny
J
Seed
Paul
P
Jones
Griff
G
Poston
Lucilla
L
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001724:Birth Weight; D002584:Cervix Uteri / Q000737:chemistry; D004311:Double-Blind Method; D005260:Female; D005353:Fibronectins / Q000032:analysis*; D005865:Gestational Age; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D008795:Metronidazole / Q000627:therapeutic use*; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011256:Pregnancy Outcome; D012307:Risk Factors; D015149:Tocolytic Agents / Q000627:therapeutic use*; D014621:Vagina / Q000737:chemistry; D016585:Vaginosis, Bacterial / Q000188:drug therapy*
D000890:Anti-Infective Agents; D015415:Biomarkers; C403421:FFN protein, human; D005353:Fibronectins; D006023:Glycoproteins; D015149:Tocolytic Agents; D008795:Metronidazole