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

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).
• 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.