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The Preterm Prediction Study: toward a multiple-marker test for spontaneous preterm birth.

R L Goldenberg, J D Iams, B M Mercer

    American Journal of Obstetrics and Gynecology
    |September 25, 2001
    PubMed
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    Combining biologic markers like fetal fibronectin, cervical length, and specific serum tests can significantly improve the prediction of spontaneous preterm birth in asymptomatic women. This approach shows promise for developing effective multiple-marker tests.

    Area of Science:

    • Obstetrics and Gynecology
    • Maternal-Fetal Medicine
    • Biomarker Discovery

    Background:

    • Spontaneous preterm birth (sPTB) remains a leading cause of neonatal morbidity and mortality.
    • Early identification of at-risk pregnancies is crucial for timely intervention.
    • The Preterm Prediction Study investigated numerous biologic markers for sPTB prediction.

    Purpose of the Study:

    • To evaluate individual and combined biologic markers for predicting spontaneous preterm birth (sPTB) at <32 and <35 weeks gestational age.
    • To assess the feasibility of developing a multiple-marker test for sPTB.

    Main Methods:

    • A nested case-control design was employed, comparing women with sPTB to matched term controls.
    • Twenty-eight potential biologic markers were analyzed, including cervical-vaginal fetal fibronectin, cervical length, and serum markers (alpha-fetoprotein, alkaline phosphatase, granulocyte colony-stimulating factor).

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  • Univariate, multivariate logistic regression, and combination analyses were performed.

    • Main Results:

    • Positive fetal fibronectin, short cervical length, and elevated serum alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor were significantly associated with sPTB.
    • Combinations of markers demonstrated substantially increased predictive power: 93% of sPTB cases had at least one positive marker (OR, 24.0).
    • Using three serum markers alone identified 81% of sPTB cases (<32 weeks) (OR, 14.7).

    Conclusions:

    • The strongest biologic markers for sPTB have limited overlap, suggesting a multi-marker approach is necessary.
    • Combining serum markers, fetal fibronectin, and cervical length can enhance sPTB prediction.
    • The development of a feasible multiple-marker test for sPTB is supported by these findings.