Reappraisal of evolving methods in non-invasive prenatal screening: Discovery, biology and clinical utility

Non-invasive prenatal screening (NIPS) offers an opportunity to screen or determine features associated with the fetus. Earlier, prenatal testing was done with cytogenetic procedures like karyotyping or fluorescence in-situ hybridization, which necessitated invasive methods such as fetal blood sampling, chorionic villus sampling or amniocentesis. Over the last two decades, there has been a paradigm shift away from invasive prenatal diagnostic methods to non-invasive ones. NIPS tests heavily rely on cell-free fetal DNA (cffDNA). This DNA is released into the maternal circulation by placenta. Like cffDNA, fetal cells such as nucleated red blood cells, placental trophoblasts, leukocytes, and exosomes or fetal RNA circulating in maternal plasma, have enormous potential in non-invasive prenatal testing, but their use is still limited due to a number of limitations. Non-invasive approaches currently use circulating fetal DNA to assess the fetal genetic milieu. Methods with an acceptable detection rate and specificity such as sequencing, methylation, or PCR, have recently gained popularity in NIPS. Now that NIPS has established clinical significance in prenatal screening and diagnosis, it is critical to gain insights into and comprehend the genesis of NIPS de novo. The current review reappraises the development and emergence of non-invasive prenatal screen/test approaches, as well as their clinical application, with a focus, on the scope, benefits, and limitations.