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Maternal urinary metabolomic signatures preceding spontaneous preterm birth: A pilot study
Manchu Umarani Thangavelu1, Emma Ronde2, Lieke Lamont1
1Metabolomics and Analytics Center, Leiden University, Einsteinweg 55, Leiden, 2333 CC, The Netherlands.
Scientific Reports
|December 4, 2025
Summary
This study identifies specific signaling lipids in urine as potential biomarkers for spontaneous preterm birth (sPTB). These novel biomarkers could improve risk prediction, helping to identify pregnancies needing intervention and avoid unnecessary treatments.
Area of Science:
- Reproductive biology
- Biomarker discovery
- Metabolomics
Background:
- Spontaneous preterm birth (sPTB) has diverse causes, complicating accurate risk prediction.
- Current methods for predicting sPTB lack sufficient accuracy, leading to misclassification in up to 40% of cases.
- Effective risk stratification is crucial for timely interventions and preventing adverse outcomes.
Purpose of the Study:
- To investigate signaling lipids in urine as potential biomarkers for spontaneous preterm birth (sPTB).
- To explore the utility of urinary metabolomics for differentiating preterm birth from term birth.
- To develop a predictive model for sPTB risk stratification.
Main Methods:
- Prospective collection of midstream urine from 30 women with imminent preterm birth.
- Retrospective classification of samples into preterm without chorioamnionitis, preterm with chorioamnionitis, and term groups.
- Analysis using liquid-chromatography mass-spectrometry to identify and quantify signaling lipids (oxylipins).
Main Results:
- Reduced levels of lipoxygenase- and cytochrome P450-derived oxylipins were observed in the preterm group, indicating impaired inflammation resolution.
- 8,9-DiHETrE and 9-HODE were identified as potential etiology-independent biomarkers for sPTB.
- A predictive model combining 9-HODE and vaginal discharge achieved an AUC of 84.2% for differentiating preterm from term delivery.
Conclusions:
- Urinary metabolomics offers a non-invasive approach to understanding sPTB pathophysiology.
- Signaling lipids, particularly 8,9-DiHETrE and 9-HODE, show promise as biomarkers for sPTB risk prediction.
- Improved risk stratification using these biomarkers can enhance clinical management of pregnancies at risk for preterm birth.

