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. DESIGN: Randomised placebo-controlled trial. SETTING: Fourteen UK hospitals (three teaching). POPULATION: 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. 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.

Fetal fibronectin test predicts delivery before 30 weeks of gestation in high risk women, but increases anxiety.

OBJECTIVE: To assess efficacy of cervico-vaginal fetal fibronectin as a predictor of spontaneous preterm birth in a high risk antenatal population, and to evaluate the psychological impact of fetal fibronectin testing. DESIGN: An observational study. SETTING: The antenatal clinic at a tertiary referral hospital. POPULATION: One hundred and forty-six pregnant women with known risk factors for spontaneous preterm birth. METHODS: Women designated as 'at risk' for preterm delivery by clinical history were screened for fetal fibronectin at 24 and again at 27 weeks of gestation. Anxiety levels were assessed by questionnaire and compared with anxiety levels of 206 low risk women also tested for fetal fibronectin. Fetal fibronectin results were disclosed to the woman and her clinician. MAIN OUTCOME MEASURES: Maternal anxiety and efficacy of the 24-week fetal fibronectin test to predict delivery before 30, 34 and 37 weeks of gestation. RESULTS: Maternal anxiety was higher pretesting in those at high risk compared with low risk women undergoing the test. Among the high risk women, anxiety was raised to clinically significant levels in those receiving a positive fetal fibronectin screening test result. In all women, 5%, 9% and 21% delivered <30, <34 or <37 weeks of gestation, respectively. Nine percent (n= 13) tested positive for fetal fibronectin at 24 weeks. Predictive power for fetal fibronectin (24 weeks) was greatest for delivery <30 weeks of gestation, with a likelihood ratio of 15 for a positive test (6/13 positive women delivered before 30 weeks). CONCLUSIONS: Fetal fibronectin was most efficient as a predictor of preterm spontaneous delivery <30 weeks of gestation, but was associated with high levels of anxiety.

Quantitative foetal fibronectin as a predictor of successful induction of labour in post-date pregnancies.

OBJECTIVE: To study the relationship between induced labour, quantitative levels of fibronectin and the Bishop score. STUDY DESIGN: Vaginal fibronectin/Bishop score were estimated in 33 nulliparous women undergoing induction of labour for post-dates at the Department of Obstetrics and Gynaecology, Guy's and St. Thomas' Hospital London. RESULTS: There was no significant relationship between either the fibronectin level or Bishop score and the duration of the latent phase (R(2)=0.001; P=0.86 and R(2)=0.12; P=0.08, respectively). There was no relationship between the total prostaglandin dose and fibronectin level (R(2)=0.03; P=0.39) nor any significant correlation between either the Bishop score or fibronectin level and the induction to delivery time (R(2)=0.13; P=0.11 and R(2)=0.0006; P=0.97, respectively). Significant relationships were observed inversely between the total prostin dose and Bishop score (R(2)=0.33; P=0.002), between the total prostin dose and latent phase (R(2)=0.54; P=0.000009) and between Bishop score and the fibronectin levels (R(2)=0.19; P<0.01). CONCLUSIONS: Quantitative foetal fibronectin is not a useful test for inducibility at term.