A Glimpse into Tomorrow:
The Development of
Non-invasive Prenatal Testing
by: Aitana Dy Macariola
In the past, couples at risk of having children with genetic conditions were concerned with prenatal diagnostics that are currently in the market. The detection of chromosomal aneuploidies were done by maternal serum marker screening and ultrasonography, which have a 2%-7% chance of having false-positive results. After doing so, invasive procedures which required taking a direct sample from the tissue of the placenta or amniotic fluid, such as amniocentesis and chorionic villus sampling were recommended for diagnosis. Overall, there are many risks associated with the current prenatal diagnosis.
Fortunately, the development of genetic technologies has rapidly increased over the past years.
With that said, a novel reproductive genetic technology will be made available in the near future.
Non-invasive pre-natal testing (NIPT) utilizes cell-free placental DNA to detect fetal chromosomal aneuploidies. In 2011, NIPT was introduced clinically in Hong Kong, then it was commercialized in the US in October of the same year. Since then, NIPT has been available commercially across the globe. It is currently available in over 60 countries on six continents. However NIPT requires a doctor’s recommendation before doing the procedure for safety reasons. On top of that while all companies screen for common chromosomal aneuploidies, the coverage of sex chromosome aneuploidies and fetal sex differs in each company and region.
NIPT provides an intermediate step between serum screening and invasive prenatal testing. It examines small DNA fragments circulating in the blood of a pregnant woman. Unlike most DNA, which is found inside the nucleus of a cell, these fragments are free-floating and not contained within cells, earning the name cell-free DNA (cfDNA). These little fragments, which consists of less than 200 DNA base pairs, form when cells die and their contents, are discharged into the circulation. The genetic status of the fetus may be assessed noninvasively using circulating cffDNA, RNA, and intact fetal cells. cffDNA is abundant, stable, and only lasts a few days in
the maternal circulation after each pregnancy, making it ideal for pregnancy-specific testing. Furthermore, new advances in DNA sequencing, such as shotgun massively parallel sequencing (MPS), make cell-free DNA sequencing in maternal circulation quicker and affordable. Changes in the quantity of fetal chromosomal DNA that signify the existence of chromosome aneuploidy may now be identified and quantified using these technologies.
Although there are still limitations and challenges in terms of its procedure and cost as to date, NIPT is a groundbreaking technology that has yet to be understood further.
Unlike invasive prenatal testings that are available on the current market, NIPT is more accurate which means there is a lower chance of false positives. Additionally, NIPT can be done at approximately 8 weeks of gestational age with no procedure related risk of miscarriage. Despite it being a better alternative compared to current prenatal tests due to its high specificity and sensitivity, professional societies still recommend that it be used as a screening method instead of a diagnostic test. Professional societies also require patients to seek the help of a genetic counselor in order to ensure that patients are able to make informed reproductive decisions.
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IMAGES:
[1] Overview of NIPT. (2021). Prenatal Screening Ontario. https://www.prenatalscreeningontario.ca/en/pso/about-prenatal-screening/overview-of-nipt.aspx
[2] Gerrish, A., Jenkinson, H., & Cole, T. (2021). The Impact of Cell-Free DNA Analysis on the Management of Retinoblastoma. Cancers, 13(7), 1570. https://doi.org/10.3390/cancers13071570