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Predictive Screening for Inflammatory Disorders of Pregnancy Using Targeted Maternal Cell-Free RNA Assays:
Sean W D Carter1, Qin Wei2, Winston Koh3
1Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road NUHS Tower Block, Level 12, Singapore, 119228, Singapore. e0983544@u.nus.edu.
Reproductive Sciences (Thousand Oaks, Calif.)
|June 4, 2025
Summary
This study developed a minimally invasive screening test using cell-free RNA (cfRNA) to detect inflammatory pregnancy complications like chorioamnionitis and pre-eclampsia early. The test accurately identified these conditions in sheep and human samples, even without clinical symptoms.
Area of Science:
- Reproductive Biology
- Molecular Diagnostics
- Genomics
Background:
- Effective management of inflammatory pregnancy complications like chorioamnionitis and pre-eclampsia is limited by the absence of early screening tools.
- Current diagnostic methods often lack the sensitivity or specificity for early detection, leading to delayed intervention.
Purpose of the Study:
- To develop and validate a minimally invasive screening test for early detection of inflammatory pregnancy complications using maternal plasma cell-free RNA (cfRNA).
- To assess the efficacy of targeted cfRNA analysis in identifying intrauterine inflammation in both animal models and human pregnancy cohorts.
Main Methods:
- Utilized a preterm sheep model to simulate sterile and bacterial chorioamnionitis, analyzing maternal plasma cfRNA.
- Employed Random Forest algorithms to identify cfRNA targets indicative of intrauterine inflammation.
- Validated cfRNA findings in human plasma samples from patients with late-onset pre-eclampsia and uncomplicated pregnancies across different trimesters.
Main Results:
- The cfRNA assay accurately identified sterile (AUC 1.0) and infectious (AUC 0.84) chorioamnionitis in the sheep model.
- Validated findings in human samples showed high accuracy for detecting pre-eclampsia in the 1st (AUC 0.85), 2nd (AUC 0.90), and 3rd (AUC 0.82) trimesters.
- The cfRNA test demonstrated high sensitivity and specificity, detecting inflammation even in the absence of overt clinical symptoms.
Conclusions:
- Targeted maternal cfRNA analysis is a promising, minimally invasive approach for early risk screening of inflammatory pregnancy complications.
- This technology has the potential to be developed into a scalable, cost-effective tool for predicting conditions like chorioamnionitis and pre-eclampsia.
- Further development could significantly improve the management and prevention of major inflammatory pregnancy disorders.
