Liquid Biopsy and Single-Cell Technologies in Maternal-Fetal Medicine: A Scoping Review of Non-Invasive Molecular Approaches

Abstract

Background: Perinatal research faces significant challenges in understanding placental biology and maternal-fetal interactions due to limited access to human tissues and the lack of reliable models. Emerging technologies, such as liquid biopsy and single-cell analysis, offer novel, non-invasive approaches to investigate these processes. This scoping review explores the current applications of these technologies in placental development and the diagnosis of pregnancy complications, identifying research gaps and providing recommendations for future studies. Methods: This review adhered to PRISMA-ScR guidelines. Studies were selected based on their focus on liquid biopsy or single-cell analysis in perinatal research, particularly related to placental development and pregnancy complications such as preeclampsia, preterm birth, and fetal growth restriction. A systematic search was conducted in PubMed, Scopus, and Web of Science for studies published in the last ten years. Data extraction and thematic synthesis were performed to identify diagnostic applications, monitoring strategies, and biomarker identification. Results: Twelve studies were included, highlighting the transformative potential of liquid biopsy and single-cell analysis in perinatal research. Liquid biopsy technologies, such as cfDNA and cfRNA analysis, provided non-invasive methods for real-time monitoring of placental function and early identification of complications. Extracellular vesicles (EVs) emerged as biomarkers for conditions like preeclampsia. Single-cell RNA sequencing (scRNA-seq) revealed cellular diversity and pathways critical to placental health, offering insights into processes such as vascular remodeling and trophoblast invasion. While promising, challenges such as high costs, technical complexity, and the need for standardization limit their clinical integration. Conclusion: Liquid biopsy and single-cell analysis are revolutionizing perinatal research, offering non-invasive tools to understand and manage complications like preeclampsia. Overcoming challenges in accessibility and standardization will be key to unlocking their potential for personalized care, enabling better outcomes for mothers and children worldwide.

Keywords: cfDNA biomarkers; extracellular vesicles; perinatal technologies; placental diagnostics; scRNA-seq placenta.

Figure 1

Liquid biopsy for placental health analysis in perinatology.

Figure 2

Extracellular vesicles (EVs) as molecular mediators in placental health.

Figure 3

Single-cell RNA sequencing (scRNA-seq) for placental health analysis.