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A Standardized Liquid Biopsy Preanalytical Protocol for Downstream Circulating-Free DNA Applications
Published on: September 16, 2022
Cell-Based and Cell-Free Non-Invasive Prenatal Analysis of Preeclampsia: An Updated Review of Liquid Biopsy
Yafeng Ma1,2,3, Ya-Wen Chiang1,2, Therese M Becker2,4
1Obstetrics Research Group, Ingham Institute for Applied Medical Research, 1 Campbell Street, Liverpool, NSW 2170, Australia.
Insights
Liquid biopsy offers a promising, less invasive method for early preeclampsia (PE) detection. Analyzing cell-free DNA, RNA, and vesicles aids in predicting and diagnosing PE, improving maternal and infant outcomes.
Area of Science:
- Obstetrics and Gynecology
- Molecular Diagnostics
- Genomics
Background:
- Preeclampsia (PE) is a serious pregnancy complication affecting 3-8% of pregnancies, leading to significant maternal and perinatal mortality.
- Untreated PE can progress to eclampsia, posing long-term health risks to both mother and child.
- Non-invasive prenatal screening using cell-free DNA (cfDNA) presents a cost-effective approach for early diagnosis.
Purpose of the Study:
- To review recent advancements in liquid biopsy techniques for preeclampsia (PE) prediction and diagnosis.
- To discuss the application of circulating fetal cells, cfDNA, cfRNA, and extracellular vesicles in understanding PE.
- To explore the evolution of liquid biopsy technologies in PE pathogenesis, prediction, and diagnosis.
Main Methods:
- Review of recent scientific literature (January 2019 - December 2025) on liquid biopsy in preeclampsia.
- Analysis of studies utilizing circulating fetal cells (trophoblasts, fetal nucleated red blood cells), cell-free DNA, cell-free RNA, and small extracellular vesicles (exosomes).
- Discussion of the conceptual framework and technical developments in liquid biopsy applications for PE.
Main Results:
- Cell-free assays, especially cfDNA and cfRNA analysis, show significant potential for early PE prediction and diagnosis.
- Liquid biopsy-derived biomarkers, including circulating fetal cells and extracellular vesicles, are crucial in understanding PE pathogenesis.
- Novel screening and diagnostic molecular biomarkers from liquid biopsies facilitate early detection in at-risk patients.
Conclusions:
- Liquid biopsy represents a powerful tool for the early detection and prediction of preeclampsia.
- Advancements in liquid biopsy technologies can lead to timely intervention and improved treatment strategies for PE.
- Non-invasive screening strategies based on liquid biopsies hold promise for reducing PE-related morbidity and mortality.
Abstract:
Preeclampsia (PE), pregnancy-associated high blood pressure linked to organ damage, affects 3-8% of all pregnancies and results worldwide in 70,000 maternal and 500,000 perinatal deaths each year. Untreated PE may progress to eclampsia with long-term health implications for both mother and child. Non-invasive prenatal diagnosis or screening applies cell-free DNA approaches and offers a less invasive and more economical method for early diagnosis and prediction of various pregnancy complications. Recently, cell-free assays, particularly blood-based cell-free DNA and RNA analysis, have shown great potential in early PE prediction and diagnosis. Here, we provide an updated review of the current understanding and discoveries of PE, focusing on recent publications (1 January 2019-30 December 2025) of liquid biopsy-derived circulating fetal cells (circulating trophoblasts and fetal nucleated red blood cells), cell-free DNA, cell-free RNA and small extracellular vesicles (i.e., exosomes). We aim to discuss the conceptual framework and technical evolution of liquid biopsy applications in preeclampsia pathogenesis, prediction and diagnosis. Progressing novel screening and diagnostic molecular biomarkers have high potential to facilitate early detection for patients at risk of PE. Liquid biopsy-based screening strategies may aid in providing timely intervention and treatment.

