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.

Biomedicines
|May 4, 2026
PubMed

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.

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