مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Next-Generation Non-Invasive Prenatal Screening: Advanced cfDNA-Based Platforms and Novel Diagnostic Kits for Early Detection of Aneuploidies and Microdeletion Syndromes
Next-Generation Non-Invasive Prenatal Screening: Advanced cfDNA-Based Platforms and Novel Diagnostic Kits for Early Detection of Aneuploidies and Microdeletion Syndromes
Kourosh Khayam Abed,1,*Sahar Masoomi,2
1. Undergraduate Student in Biotechnology, Naqsh-e Jahan University, Isfahan, Iran 2. Researcher in Medical Genetics, Medical and Pharmaceutical Biotechnology, Neurogenomics and Translational Neuroscience, Applied Artificial Intelligence, Pharmacogenomics, and Psychology
Introduction: In recent years, non-invasive prenatal testing (NIPT) based on sequencing of cell-free fetal DNA (cffDNA) in maternal plasma has become a global standard for screening chromosomal abnormalities. These methods have demonstrated exceptional performance in detecting common trisomies 21, 18, and 13, with sensitivity above 99% and false-positive rates below 0.5% in large populations, including millions of pregnancies in Europe and North America. Between 2012 and 2022, over 10 million pregnancies worldwide underwent NIPT, resulting in a marked reduction in the use of invasive procedures such as amniocentesis and a corresponding decrease in procedure-related miscarriage risk.
The discovery of cffDNA has not only enabled accurate screening for common trisomies but has also facilitated the detection of rare subchromosomal alterations, including microdeletions and copy number variations (CNVs), as well as the analysis of single genes in certain monogenic disorders. Current NIPT platforms leverage advanced molecular technologies, including next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), to analyze and quantify fetal genetic material with unprecedented precision. Biochemical features of cffDNA, such as fragment size, methylation patterns, and placental origin, allow differentiation of fetal DNA from maternal DNA and enhance diagnostic accuracy.
Recent advances have expanded the scope of NIPT to include detection of single-gene disorders and rare subchromosomal variations previously identifiable only through invasive methods. Integration of automated cell isolation platforms, such as self-assembling cell array (SACA) chips, enables enrichment and analysis of rare nucleated fetal cells from maternal circulation and, when combined with cffDNA testing, increases diagnostic yield for complex or mosaic chromosomal disorders.
Despite these innovations, technical and clinical challenges remain. Factors such as low fetal fraction, maternal DNA contamination, placental mosaicism, and multiple gestations can affect test sensitivity and specificity. Moreover, analytical validation of novel cffDNA-based diagnostic kits for early pregnancy requires careful evaluation of performance metrics, including limit of detection, positive predictive value, and reproducibility across diverse populations.
Given these developments, current prenatal genetic screening is moving toward next-generation non-invasive platforms that integrate high-throughput sequencing, multi-omic analyses, and automated cell enrichment to enable early and accurate detection of both common and rare fetal genomic abnormalities. This review focuses on the latest cffDNA-based NIPT platforms, emerging diagnostic kits, and their clinical implications, providing a comprehensive framework for next-generation non-invasive screening strategies while highlighting the opportunities and limitations for clinical implementation.
Methods: This systematic review analyzed recent advancements in cffDNA-based NIPT platforms. Systematic searches were conducted in PubMed, Scopus, and Web of Science (2019–2025) using keywords related to NIPT, cffDNA, aneuploidies, microdeletions, and next-generation sequencing.
Included studies reported clinical and analytical performance metrics (sensitivity, specificity, predictive values) across diverse pregnant populations. Extracted data included platform type, sample size, gestational age, fetal DNA fraction, and diagnostic performance. Technical and clinical limitations, such as low fetal fraction, maternal DNA contamination, and multiple pregnancies, were also evaluated to compare next-generation NIPT performance and clinical implications.
Results: Next-generation cffDNA-based NIPT platforms with advanced diagnostic kits enable rapid, accurate screening of fetal chromosomal and subchromosomal abnormalities. Using NGS and automated cell enrichment, they detect low fetal DNA quantities in maternal samples with high sensitivity and precision, reducing reliance on invasive methods.
Novel kits simplify sample preparation and analysis, shortening turnaround time and supporting large-scale screening across diverse populations. Clinical studies report >99% sensitivity and significantly reduced false-positive rates. Automation decreases technical expertise requirements, enhancing efficiency and enabling deployment in high-risk or underserved populations without compromising accuracy or safety.
Conclusion: The integration of next-generation NIPT platforms with lightweight, cost-effective diagnostic kits represents a novel approach to prenatal genetic screening within the field of medical biotechnology. These technologies allow early, rapid, and precise detection of chromosomal and subchromosomal fetal abnormalities while reducing reliance on traditional invasive procedures and optimizing cost and turnaround time.
Future perspectives include the development of portable kits and devices, improved diagnostic accuracy, cost reduction, and broader accessibility of genetic screening across diverse populations and clinical environments. This approach advances the integration of cutting-edge biotechnology with clinical care, elevating the early detection and prevention of genetic disorders to a new level.