AACC Guidance Document on Laboratory Testing for the Assessment of Preterm Delivery

Area of Science:

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

Background:

• Identifying women in preterm labor who will deliver prematurely is critical for maternal and infant outcomes and healthcare resource management.
• Existing biomarkers for preterm birth (PTB) have low positive predictive value (PPV) and high negative predictive value (NPV), offering limited clinical certainty.
• Biomarkers such as fetal fibronectin (fFN), interleukin-6 (IL-6), and placental alpha microglobulin 1 (PAMG-1) show some promise but are unlikely to be clinically valuable in low-prevalence populations.

Purpose of the Study:

• To evaluate the clinical utility of current biomarkers for predicting preterm birth (PTB) in symptomatic women.
• To determine if any biomarkers can achieve a high PPV necessary for identifying women likely to deliver prematurely.
• To recommend appropriate use of biomarkers based on pre-test probability and clinical characteristics.

Main Methods:

• Review and analysis of existing data on biomarkers for PTB prediction, including fFN, IL-6, and PAMG-1.
• Assessment of biomarker performance metrics, focusing on PPV and NPV in relation to pre-test probability.
• Evaluation of strategies to improve biomarker utility, such as targeted testing in high-risk populations.

Main Results:

• Current biomarkers, including fFN, IL-6, and PAMG-1, do not exhibit the high PPV required for effective clinical use in populations with a low pre-test probability (<5%) of PTB.
• The low PPV of available biomarkers does not substantially reduce diagnostic uncertainty for preterm labor.
• PAMG-1 demonstrates a higher PPV compared to fFN, suggesting potential utility in higher pre-test probability groups, though further research is needed.

Conclusions:

• Routine clinical use of current PTB biomarkers is not recommended for populations with a pre-test probability below 5%.
• Targeting biomarker testing to high-risk women, identified by factors like cervical length, can increase pre-test probability and improve PPV.
• Further research is necessary to confirm the clinical utility and impact on outcomes of PAMG-1 in selected high-risk populations.