Cell-Free Fetal Deoxyribonucleic Acid (cffDNA) Analysis as a Remarkable Method of Non-Invasive Prenatal Screening

Abstract

The cell-free fetal DNA (cffDNA) analysis for screening fetal genetic anomalies has increased dramatically since its commercialization in 2011 worldwide. In the early weeks of pregnancy, it offers a hassle-free, noninvasive procedure of antenatal screening. It guides and protects mothers from undergoing unwanted riskladen invasive prenatal testing. cffDNA testing is accurate at detecting the abnormal fetus chromosome among a large pool population. Patau syndrome, Edward syndrome, and Down syndrome are currently being accurately screened by this method. Due to their sensitivity and specificity, they now have become the screening method of choice, approaching almost 100% in various studies with a large sample pool. The latest procedures to analyze cffDNA, like the new digital droplet polymerase chain reaction (ddPCR) and sophisticated next-generation sequencing (NGS), have increased detection rates with decreased analyzing time. The latest techniques make it possible to screen large numbers of the population with faster report generation. Screening for Rh incompatibility and its timely prevention is now more accessible and more accurate with the help of cffDNA analysis. The problem arises when we deviate from the primary disease and start testing for anomalies not intended to be screened by cffDNA in the first place. Fetal sex chromosome aneuploidy screening by cffDNA is one area where the test gives mixed results either due to differences in machinery, laboratory parameters, or human error. Other rare occurrences like trisomes, such as trisomy 7, trisomy 16, trisomy 22, and a few microdeletion syndromes are also being screened but with less accuracy. Like every technology, cffDNA analysis is not entirely free of criticism. Its high testing cost, potential to accurately prognosticate the gender of the developing fetus and absence of standard testing practices will become an issue as the test becomes routine worldwide.

Non-Invasive Prenatal Testing (NIPT): Reliability, Challenges, and Future Directions

“…In addition to its purpose as a biomarker in forecasting obstetrics cases such as preeclampsia [14], monogenic disorders [15], and placenta accreta [16,17], cffDNA is invaluable for the analysis and detection of foetal chromosomal abnormalities during the early phase of pregnancy [18,19]. NIPT is a non-invasive prenatal screening technique performed using next-generation sequencing (NGS) to sequence short cffDNA fragments in order to identify the genetic variants that represent chromosomal abnormalities.…”

DNA Methylation in the Fields of Prenatal Diagnosis and Early Detection of Cancers

“…It means current NIPTs that are in use are not reviewed by the FDA [64]. Nevertheless, the cffDNA-based NIPTs are recognized as the most efficient prenatal screening option to detect genetic abnormalities and the most common serious chromosomal diseases in the fetus such as trisomy 13, trisomy 18 and trisomy 21 [65]. In 2023, the International Society for Prenatal Diagnosis (ISPD) reported its latest public position statement on NIPTs for fetal chromosomal conditions in singleton pregnancies, replacing their earlier statement published in 2015 [66].…”