Am J Perinatol 2011; 28(2): 145-150
DOI: 10.1055/s-0030-1263297
© Thieme Medical Publishers

Why Were the Results of Randomized Trials on the Clinical Utility of Fetal Fibronectin Negative? A Systematic Review of Their Study Designs

Jolande Y. Vis1 , Femke F. Wilms2 , Martijn A. Oudijk3 , Patrick M.M. Bossuyt4 , Joris A.M. van der Post1 , William A. Grobman5 , Ben Willem J. Mol1
  • 1Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam
  • 2Department of Obstetrics and Gynecology, Máxima Medical Center, Veldhoven
  • 3Department of Obstetrics and Gynecology, University Medical Center Utrecht, Utrecht
  • 4Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
  • 5Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, Illinois
Further Information

Publication History

Publication Date:
12 August 2010 (online)

ABSTRACT

Randomized trials on the clinical utility of fetal fibronectin in women with symptoms of preterm labor have thus far failed to demonstrate benefits. We systematically reviewed the methodology of these trials to assess if these negative results may be related to their study designs. We searched the literature for randomized trials that evaluated fibronectin testing in women with symptoms of preterm labor. Study results were evaluated and five methodological criteria were assessed: (1) randomization of discordant test results, (2) use of a fixed management protocol, (3) description of interventions in relation to the test result, (4) evaluation of a learning curve, and (5) sample size calculation in agreement with the prevalence of the test results. We detected four randomized trials that met inclusion criteria. All trials allocated women to a strategy with or without availability of fibronectin results without using a discordancy design or a fixed management protocol. One study reported the given treatment in relation to the test results. Learning curves were evaluated in one study. Two studies used transport sample size calculations. The negative results of randomized trials on fetal fibronectin may be due to particular choices in their study design.

REFERENCES

  • 1 Slattery M M, Morrison J J. Preterm delivery.  Lancet. 2002;  360 1489-1497
  • 2 Papatsonis D N, Van Geijn H P, Adèr H J, Lange F M, Bleker O P, Dekker G A. Nifedipine and ritodrine in the management of preterm labor: a randomized multicenter trial.  Obstet Gynecol. 1997;  90 230-234
  • 3 McPheeters M L, Miller W C, Hartmann K E et al.. The epidemiology of threatened preterm labor: a prospective cohort study.  Am J Obstet Gynecol. 2005;  192 1325-1329 discussion 1329-1330
  • 4 Campbell M K, Challis J R, DaSilva O, Bocking A D. A cohort study found that white blood cell count and endocrine markers predicted preterm birth in symptomatic women.  J Clin Epidemiol. 2005;  58 304-310
  • 5 French N P, Hagan R, Evans S F, Mullan A, Newnham J P. Repeated antenatal corticosteroids: effects on cerebral palsy and childhood behavior.  Am J Obstet Gynecol. 2004;  190 588-595
  • 6 Oei S G, Oei S K, Brölmann H A. Myocardial infarction during nifedipine therapy for preterm labor.  N Engl J Med. 1999;  340 154
  • 7 van Veen A J, Pelinck M J, van Pampus M G, Erwich J J. Severe hypotension and fetal death due to tocolysis with nifedipine.  BJOG. 2005;  112 509-510
  • 8 Lockwood C J, Senyei A E, Dische M R et al.. Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery.  N Engl J Med. 1991;  325 669-674
  • 9 Matsuura H, Takio K, Titani K et al.. The oncofetal structure of human fibronectin defined by monoclonal antibody FDC-6. Unique structural requirement for the antigenic specificity provided by a glycosylhexapeptide.  J Biol Chem. 1988;  263 3314-3322
  • 10 Honest H, Bachmann L M, Gupta J K, Kleijnen J, Khan K S. Accuracy of cervicovaginal fetal fibronectin test in predicting risk of spontaneous preterm birth: systematic review.  BMJ. 2002;  325 301
  • 11 Revah A, Hannah M E, Sue-A-Quan A K. Fetal fibronectin as a predictor of preterm birth: an overview.  Am J Perinatol. 1998;  15 613-621
  • 12 Sanchez-Ramos L, Delke I, Zamora J, Kaunitz A M. Fetal fibronectin as a short-term predictor of preterm birth in symptomatic patients: a meta-analysis.  Obstet Gynecol. 2009;  114 631-640
  • 13 Berghella V, Hayes E, Visintine J, Baxter J K. Fetal fibronectin testing for reducing the risk of preterm birth.  Cochrane Database Syst Rev. 2008;  (4) CD006843
  • 14 Bossuyt P M, Lijmer J G, Mol B W. Randomised comparisons of medical tests: sometimes invalid, not always efficient.  Lancet. 2000;  356 1844-1847
  • 15 Bossuyt P M, Reitsma J B, Bruns D E Standards for Reporting of Diagnostic Accuracy et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Standards for Reporting of Diagnostic Accuracy.  Clin Chem. 2003;  49 1-6
  • 16 Moher D, Schulz K F, Altman D. CONSORT Group (Consolidated Standards of Reporting Trials) . The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials.  JAMA. 2001;  285 1987-1991
  • 17 McShane L M, Altman D G, Sauerbrei W, Taube S E, Gion M, Clark G M. Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics . Reporting recommendations for tumor marker prognostic studies (REMARK).  J Natl Cancer Inst. 2005;  97 1180-1184
  • 18 Altman D G. Systematic reviews of evaluations of prognostic variables.  BMJ. 2001;  323 224-228
  • 19 Guyatt G H, Tugwell P X, Feeny D H, Haynes R B, Drummond M. A framework for clinical evaluation of diagnostic technologies.  CMAJ. 1986;  134 587-594
  • 20 Grobman W A, Welshman E E, Calhoun E A. Does fetal fibronectin use in the diagnosis of preterm labor affect physician behavior and health care costs? A randomized trial.  Am J Obstet Gynecol. 2004;  191 235-240
  • 21 Lowe M P, Zimmerman B, Hansen W. Prospective randomized controlled trial of fetal fibronectin on preterm labor management in a tertiary care center.  [see comment] Am J Obstet Gynecol. 2004;  190 358-362
  • 22 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;  197 426-427, e1–e7
  • 23 Plaut M M, Smith W, Kennedy K. Fetal fibronectin: the impact of a rapid test on the treatment of women with preterm labor symptoms.  Am J Obstet Gynecol. 2003;  188 1588-1593 discussion 1593-1595
  • 24 Vis J Y, Wilms F F, Oudijk M A et al.. Cost-effectiveness of fibronectin testing in a triage in women with threatened preterm labor: alleviation of pregnancy outcome by suspending tocolysis in early labor (APOSTEL-I trial).  BMC Pregnancy Childbirth. 2009;  9 38

Jolande Y VisM.D. M.Sc. 

Department of Obstetrics and Gynecology, Academic Medical Center

P.O. Box 22660, 1100 DD Amsterdam, The Netherlands

Email: j.y.vis@amc.nl