Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized controlled trials

Published:April 28, 2016DOI:

      Objective Data

      Fetal fibronectin is an extracellular matrix glycoprotein that is produced by amniocytes and cytotrophoblasts and has been shown to predict spontaneous preterm birth.


      The aim of this systematic review and metaanalysis of randomized clinical trials was to evaluate the effect of the use of fetal fibronectin in the prevention of preterm birth in singleton pregnancies with threatened preterm labor.

      Study Appraisal and Synthesis Methods

      The research was conducted with the use of MEDLINE, EMBASE, Web of Sciences, Scopus,, OVID, and Cochrane Library as electronic databases from the inception of each database to February 2016. Selection criteria included randomized clinical trials of singleton gestations with threatened preterm labor that were assigned randomly to management based on fetal fibronectin results (ie, intervention group) or not (ie, comparison group). Types of participants included women with singleton gestations at 23 0/7 to 34 6/7 weeks with threatened preterm labor. Studies that included management that was also based on the use of sonographic cervical length were excluded. The primary outcome was preterm birth at <37 weeks of gestation. The summary measures were reported as relative risk or as mean differences with 95% confidence interval.


      Six trials that included 546 singleton gestations with symptoms of preterm labor were included in the metaanalysis. The overall risk of bias of the included trials was low. Women were eligible for the random assignment in case of symptoms that suggested preterm labor at 23–34 weeks of gestation. During admission, before digital examination, a Dacron swab was rotated in the posterior fornix for 10 seconds to absorb cervicovaginal secretions that were then analyzed for the fetal fibronectin qualitative method, with results reported as either positive or negative. Women who were assigned randomly to the fetal fibronectin group had a similar incidence of preterm birth at <37 weeks of gestation (20.7% vs 29.2%; relative risk, 0.72; 95% confidence interval, 0.52–1.01), at <34 weeks of gestation (8.3% vs 7.9%; relative risk, 1.09; 95% confidence interval, 0.54–2.18), at <32 weeks of gestation (3.3% vs 5.6%; relative risk, 0.64; 95% confidence interval, 0.24–1.74), and at <28 weeks of gestation (1.1% vs 1.7%; relative risk, 0.74; 95% confidence interval, 0.15–3.67) compared with the control group. No differences were found in the number of women who delivered within 7 days (12.8% vs 14.5%; relative risk, 0.76; 95% confidence interval, 0.47–1.21), in the mean of gestational age at delivery (mean difference, 0.20 week; 95% confidence interval, –0.26 to 0.67), in the rate of maternal hospitalization (27.4% vs 26.9%; relative risk, 1.07; 95% confidence interval, 0.80–1.44), in the use of tocolysis (25.3% vs 28.2%; relative risk, 0.97; 95% confidence interval, 0.75–1.24), antenatal steroids (29.2% vs 29.2%; relative risk, 1.05; 95% confidence interval, 0.79–1.39), in the mean time in the triage unit (mean difference, 0.60 hour; 95% confidence interval, –0.03 to 1.23) and in neonatal outcomes that included respiratory distress syndrome (1.3% vs 1.5%; relative risk, 0.91; 95% confidence interval, 0.06–14.06), and admission to the neonatal intensive care unit (19.4% vs 8.1%; relative risk, 2.48; 95% confidence interval, 0.96–6.46). Management based on the fetal fibronectin test required higher hospitalization charges (mean difference, $153; 95% confidence interval, 24.01–281.99).


      Fetal fibronectin testing in singleton gestations with threatened preterm labor is not associated with the prevention of preterm birth or improvement in perinatal outcome but is associated with higher costs.

      Key words

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      Linked Article

      • Randomized clinical trials are not always the best way to assess diagnostic tests: the case of fetal fibronectin testing
        American Journal of Obstetrics & GynecologyVol. 218Issue 1
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          Recently, Berghella and Saccone1 published in this journal a meta-analysis on fetal fibronectin as predictor of preterm birth. In this meta-analysis, the authors concluded that women assigned randomly to the knowledge of fibronectin results did not have reduced preterm birth rates compared to a control group. In addition, both groups had similar rates of hospitalization, and use of tocolytics and steroids. Mean hospital costs were even slightly higher in the fetal fibronectin group. This conclusion was based on 6 randomized clinical trials (RCTs) reporting on 546 women with threatened preterm labor; 13% of the included delivered within 1 week after presentation.
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