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      We thank van Baaren et al for their letter and their interest in our study on fetal fibronectin (FFN) for management of women with preterm labor (PTL) at around 23-34 weeks.
      • Berghella V.
      • Saccone G.
      Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized controlled trials.
      We congratulate their group for having done important work in this area, and confirmed themselves the good prediction of transvaginal ultrasound (TVU) cervical length (CL) in combination with FFN for prediction of preterm birth (PTB) in women with threatened PTL.
      • Hermans F.J.
      • Bruijn M.M.
      • Vis J.Y.
      • et al.
      Risk stratification with cervical length and fetal fibronectin in women with threatened preterm labor before 34 weeks and not delivering within 7 days.
      • Bruijn M.M.
      • Kamphuis E.I.
      • Hoesli I.M.
      • et al.
      The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women.
      • van Baaren G.J.
      • Vis J.Y.
      • Wilms F.F.
      • et al.
      Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor.
      • van Baaren G.J.
      • Vis J.Y.
      • Wilms F.F.
      • et al.
      Cost-effectiveness of diagnostic testing strategies including cervical length measurement and fibronectin testing in women with symptoms of preterm labor.
      We agree that a test, eg, FFN, by itself would not prevent the outcome, eg, PTB. Nonetheless, if a test is done, one must be ready with a therapy for that test in case it is positive. It’s like ordering a cholesterol level for a patient, and hoping it comes back negative. The test may come back positive, and it would not be helpful to just say to the patient, “Given your high cholesterol level, you are at high risk for a heart attack. Good-bye.” Same is true of FFN. If the FFN comes back high (ie, positive), the obstetric provider cannot just say, “Given your high FFN level, you are at high risk for delivering preterm. Good-bye.” This would be not only unhelpful, but detrimental, as it would just increase the stress level of a woman already having discomfort from threatened PTL. Unfortunately, while several interventions are available for a patient with high cholesterol (eg, change in diet, exercise, medications), no intervention (little research has been done in this area) has been shown to be beneficial for a positive FFN.
      • Shennan A.
      • Crawshaw S.
      • Briley A.
      • et al.
      A randomized controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study.
      van Baaren et al make the case nonetheless that FFN use in women with PTL would perhaps save utilization of resources. As they state in their letter, maternal hospitalization, administration of tocolysis, administration of steroids for fetal maturity, time in triage, and hospitalization costs were not lower in the FFN group compared to controls in whom FFN was not used in our meta-analysis.
      • Berghella V.
      • Saccone G.
      Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized controlled trials.
      In fact, hospitalization charges were $153 significantly higher in the FFN group.
      • Berghella V.
      • Saccone G.
      Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized controlled trials.
      Neither the Society for Maternal-Fetal Medicine (SMFM),

      SMFM. PTB toolkit. Available at: https://www.smfm.org/publications/231-smfm-preterm-birth-toolkit. Accessed Sept. 6, 2017.

      nor the American Congress of Obstetricians and Gynecologists,
      American College of Obstetricians and Gynecologists
      Management of preterm labor. ACOG Practice bulletin no. 127.
      recommend FFN use alone for women with threatened PTL.
      We agree with van Baaren et al that the way forward involves TVU CL in the management of women with threatened PTL. Their group has shown that, in women with threatened PTL, a TVU CL <15 mm is consistent with a high risk for PTB and warrants interventions (eg, hospitalization, steroids, and possibly tocolysis); a TVU CL ≥30 mm is associated with a very low risk of PTB within 7 days (<2%) and therefore these women can be discharged, while FFN can be best used for women with a “borderline” TVU CL of 15-30 mm.
      • van Baaren G.J.
      • Vis J.Y.
      • Wilms F.F.
      • et al.
      Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor.
      Their group has indeed shown this management strategy is cost-effective.
      • van Baaren G.J.
      • Vis J.Y.
      • Wilms F.F.
      • et al.
      Cost-effectiveness of diagnostic testing strategies including cervical length measurement and fibronectin testing in women with symptoms of preterm labor.
      Randomized studies and meta-analyses of these trials have been done using this strategy of mainly TVU CL screening for evaluating women with threatened PTL, with FFN only for borderline TVU CL measurements.
      • Ness A.
      • Visintine J.
      • Ricci E.
      • Berghella V.
      Does knowledge of cervical length and fetal fibronectin affect management of women with threatened preterm labor? A randomized trial.
      • Berghella V.
      • Palacio M.
      • Ness A.
      • Alfirevic Z.
      • Nicolaides K.H.
      • Saccone G.
      Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.
      The most informative studies are, as van Baaren et al point out, those using a management protocol (Figure).
      • Ness A.
      • Visintine J.
      • Ricci E.
      • Berghella V.
      Does knowledge of cervical length and fetal fibronectin affect management of women with threatened preterm labor? A randomized trial.
      The management protocol in the Figure has indeed been associated in a randomized trial and a meta-analysis of randomized trials with a significant decrease in PTB <37 weeks.
      • Ness A.
      • Visintine J.
      • Ricci E.
      • Berghella V.
      Does knowledge of cervical length and fetal fibronectin affect management of women with threatened preterm labor? A randomized trial.
      • Berghella V.
      • Palacio M.
      • Ness A.
      • Alfirevic Z.
      • Nicolaides K.H.
      • Saccone G.
      Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.
      We encourage the reader to download the free “SMFM PTB toolkit” (type these words in the App store) App

      SMFM. PTB toolkit. Available at: https://www.smfm.org/publications/231-smfm-preterm-birth-toolkit. Accessed Sept. 6, 2017.

      SMFM. Preterm birth toolkit App. Available at: https://www.smfm.org/ptbtoolkit. Accessed Sept. 6, 2017.

      on their iPhone (Apple, Cupertino, CA) or any Android device for easy use of this protocol during their clinical management of women with threatened PTL.
      Figure thumbnail gr1
      FigureSuggested management algorithm for women presenting with threatened preterm labor
      Suggested algorithm for management of threatened preterm labor (PTL) in women with cervix <3 cm dilated on initial manual exam.

      SMFM. PTB toolkit. Available at: https://www.smfm.org/publications/231-smfm-preterm-birth-toolkit. Accessed Sept. 6, 2017.

      CL, cervical length; CTX, contractions; FFN, fetal fibronectin; TVU, transvaginal ultrasound.
      Berghella. RCTs for FFN. Am J Obstet Gynecol 2018.

      References

        • Berghella V.
        • Saccone G.
        Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized controlled trials.
        Am J Obstet Gynecol. 2016; 215: 431-438
        • Hermans F.J.
        • Bruijn M.M.
        • Vis J.Y.
        • et al.
        Risk stratification with cervical length and fetal fibronectin in women with threatened preterm labor before 34 weeks and not delivering within 7 days.
        Acta Obstet Gynecol Scand. 2015; 94: 715-721
        • Bruijn M.M.
        • Kamphuis E.I.
        • Hoesli I.M.
        • et al.
        The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women.
        Am J Obstet Gynecol. 2016; 215: 793.e1-793.e8
        • van Baaren G.J.
        • Vis J.Y.
        • Wilms F.F.
        • et al.
        Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor.
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        • van Baaren G.J.
        • Vis J.Y.
        • Wilms F.F.
        • et al.
        Cost-effectiveness of diagnostic testing strategies including cervical length measurement and fibronectin testing in women with symptoms of preterm labor.
        Ultrasound Obstet Gynecol. 2017;
        • Shennan A.
        • Crawshaw S.
        • Briley A.
        • et al.
        A randomized 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
      1. SMFM. PTB toolkit. Available at: https://www.smfm.org/publications/231-smfm-preterm-birth-toolkit. Accessed Sept. 6, 2017.

        • American College of Obstetricians and Gynecologists
        Management of preterm labor. ACOG Practice bulletin no. 127.
        Obstet Gynecol. 2012; 119: 1308-1317
        • Ness A.
        • Visintine J.
        • Ricci E.
        • Berghella V.
        Does knowledge of cervical length and fetal fibronectin affect management of women with threatened preterm labor? A randomized trial.
        Am J Obstet Gynecol. 2007; 197: 426.e1-426.e7
        • Berghella V.
        • Palacio M.
        • Ness A.
        • Alfirevic Z.
        • Nicolaides K.H.
        • Saccone G.
        Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.
        Ultrasound Obstet Gynecol. 2017; 49: 322-329
      2. SMFM. Preterm birth toolkit App. Available at: https://www.smfm.org/ptbtoolkit. Accessed Sept. 6, 2017.

      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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