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Comparison of Fetal Fibronectin and Phosphorylated Insulin-Like Growth Factor Binding Protein-1 Testing to Predict Preterm Delivery in Symptomatic Women: A 10-Year Retrospective Study

  • Michael X. Chen
    Correspondence
    Corresponding author: Dr. Michael Chen
    Affiliations
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC

    Department of Laboratory Medicine, Pathology, and Medical Genetics, Vancouver Island Health Authority, Victoria, BC

    Division of Medical Sciences, University of Victoria, Victoria, BC
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  • Jerome Dansereau
    Affiliations
    Division of Medical Sciences, University of Victoria, Victoria, BC

    Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC
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  • Gordon N. Hoag
    Affiliations
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC

    Department of Laboratory Medicine, Pathology, and Medical Genetics, Vancouver Island Health Authority, Victoria, BC
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Published:April 25, 2020DOI:https://doi.org/10.1016/j.jogc.2020.01.021

      Abstract

      Objective

      To assess the diagnostic accuracy and cost-effectiveness of fetal fibronectin (fFN) and cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) tests, individually and in combination, to predict preterm delivery within 48 hours, 7 days and 14 days in symptomatic women.

      Method

      We selected women in Victoria, British Columbia, who presented between January 2008 and December 2017 at <34 weeks gestation at intermediate risk for labour (intact membrane, cervical dilatation <3 cm, and >6 contractions per hour). We calculated sensitivity, specificity, and positive and negative predictive values (PPV, NPV) for independent and concurrent testing and conducted a cost-effectiveness analysis to ensure appropriate test utilization.

      Results

      We identified 2911 cases. Both fFN and phIGFBP-1 tests showed high and comparable NPV in predicting risk of delivery within 48 hours, 7 days and 14 days (fFN: 99.3%, 98.5% and 97.3%; phIGFBP-1: 98.8%, 97.9% and 96.1%). In 1976 cases, samples for fFN and phIGFBP-1 tests were collected and analyzed concurrently. Concurrent analysis increased specificity (90.8%, 91.4%, and 91.8%) and PPV (11.8%, 19.8% and 24.2%). Independently, both tests had comparable sensitivity, while the fFN test had higher specificity. Concurrent testing offered the highest PPV. The net gain in PPV comes with a clinically insignificant net loss (<1%) in NPV when compared with either of the tests individually.

      Conclusion

      Clinical usefulness of PPV for either test is limited. Routine concurrent testing comes with additional costs, and fFN has additional collection requirements. Point-of-care phIGFBP-1 testing has proven to be cheaper, simpler, and equally effective. Ordering physicians should be provided with education on how to interpret test results and should have protocols to guide clinical decision making.

      Résumé

      Objectif

      Évaluer l'exactitude et le rapport coût-efficacité des tests de détection de la fibronectine fœtale (FNf) de l’insulin-like growth factor binding protein-1 phosphorylée (IGFBP-1ph) cervicale, indépendamment ou en association, utilisés pour prédire l'accouchement prématuré dans les 48 heures, les 7 jours et les 14 jours chez les femmes symptomatiques.

      Méthode

      Nous avons sélectionné des femmes à Victoria, en Colombie-Britannique, à <34 SA qui manifestaient un risque intermédiaire de travail prématuré (membranes intactes, dilatation du col <3 cm et >6 contractions par heure), dans la période de janvier 2008 à décembre 2017. Nous avons calculé la sensibilité, la spécificité ainsi que les valeurs prédictives positives et négatives (VPP et VPN) pour les tests de détection utilisés indépendamment ou en association, puis effectué une analyse coût-efficacité pour veiller à l'utilisation appropriée des tests.

      Résultats

      Nous avons recensé 2 911 cas. Les deux tests de détection (FNf et IGFBP-1ph) ont obtenu des VPN élevées et comparables pour la prédiction du risque d'accouchement dans les 48 heures, les 7 jours et les 14 jours (FNf : 99,3 %, 98,5 % et 97,3 %; IGFBP-1ph : 98,8 %, 97,9 % et 96,1 %). Dans 1 976 cas, les échantillons ont été prélevés pour les tests de détection de la FNf et de l'IGFBP-1ph puis analysés simultanément. L'analyse simultanée a augmenté la spécificité (90,8 %, 91,4 % et 91,8 %) et la VPP (11,8 %, 19,8 % et 24,2 %). Individuellement, les deux tests de détection ont eu une sensibilité comparable, tandis que le test de détection de la FNf a obtenu une meilleure spécificité. Les tests de détection réalisés simultanément ont obtenu la meilleure VPP. Le gain net en VPP s'accompagne d'une perte nette cliniquement négligeable (<1 %) en VPN par comparaison à chacun des tests utilisés individuellement.

      Conclusion

      L'utilité clinique de la VPP pour un ou l'autre des deux tests de détection est limitée. La détection simultanée systématique entraîne des coûts supplémentaires, et la détection de la FNf comporte des exigences de prélèvement supplémentaires. Le test de détection de l'IGFBP-1ph au point de service s'est révélé plus économique, plus simple et aussi efficace que le test de détection de la FNf. Il y a lieu de fournir aux médecins qui demandent les tests la formation nécessaire sur la façon d'interpréter les résultats; de même, il y a lieu d’établir des protocoles pour orienter le processus décisionnel clinique.

      Keywords

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