Noninvasive prenatal testing
Non invasive prenatal testing | |
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Other names | NIPT |
Specialty | Medical diagnosis, Obstetrics and gynaecology |
Non invasive prenatal testing is a method used to determine the risk for the fetus being born with certain chromosomal abnormalities, such as Trisomy 21, Trisomy 18 and Trisomy 13.[1][2][3] This testing analyzes small DNA fragments that circulate in the blood of a pregnant woman.[4] Unlike most DNA found in the nucleus of a cell, these fragments are not found within the cells, instead they are free-floating, and so are called cell free fetal DNA (cffDNA). These fragments usually contain less than 200 DNA building blocks (base pairs) and arise when cells die, and their contents, including DNA, are released into the bloodstream. cffDNA derives from placental cells and is usually identical to fetal DNA. Analysis of cffDNA from placenta provides the opportunity for early detection of certain chromosomal abnormalities without harming the fetus.[5]
Background
The use of ultrasound and biochemical markers to detect aneuploidies is usually done in the first and / or second trimester of pregnancy. However, both of these approaches have a high rate of false positive results of 2-7%.[6] If these tests indicate an increased risk of aneuploidy, then invasive diagnostic testing is used, such as amniocentesis or chorionic villus sampling. Many women, however, feel uncomfortable with the invasive testing, because of the risk associated with miscarriage, which is around 1%. Non-invasive prenatal testing is an intermediate step between prenatal screening and invasive diagnostic testing. The only physical risk associated with the procedure is the blood draw and there is no risk of miscarriage.[7]
Circulating cffDNA can be detected in maternal blood between the 5th and the 7th week of gestational age,[8] however more fetal DNA is available for analysis usually after 10 weeks, because the amount of fetal DNA increases over time.[9] cffDNA, RNA and intact fetal cells can all be used to assess the genetic status of the fetus non-invasively. Recent advances in DNA sequencing, such as massive parallel sequencing (MPS) and digital polymerase chain reaction (PCR), are currently under exploration for the detection of chromosomal aneuploidies via NIPT.[10][11][12][13]
Since 2014, non invasive testing has identified aneuploidies in chromosomes 13, 16, 18, 21, 22, X and Y, including Down syndrome (caused by trisomy 21), Edwards syndrome (caused by trisomy 18), Patau syndrome (caused by trisomy 13), as well as sex chromosomes aneuploidies, such as Turner syndrome (45, X) and Klinefelter syndrome (47, XXY).[14][15][16] These methods of cffDNA sequencing have sensitivity and specificity rates greater than 99% in identifying Trisomy 21. Sensitivity and specificity rates are lower for other aneuploidies, such as Trisomy 18 (97-99% and > 99%, respectively), Trisomy 13 (87-99% and > 99%, respectively), and 45, X (92-95% and 99%, respectively). The low false positive rate (1-3%) is one of the advantages of NIPT which allows pregnant women to avoid invasive procedures.[17]
NIPT can determine paternity and fetal sex earlier in gestation than previous tests (including possibly ultrasound).[18] It is also used to determine fetal Rhesus D, which can prevent mothers who are Rhesus D negative from undergoing unnecessary prophylactic treatment.[19][20] Finally, it is used to detect genetic mutations, such as duplications or microdeletions, including 1p, 5p, 15q, 22q, 11q, 8q, and 4p. The sensitivity and specificity of these tests, however, has not yet been validated.[7]
References
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- ^ Goldwaser, Tamar; Klugman, Susan (2018). "Cell-free DNA for the detection of fetal aneuploidy". Fertility and Sterility. 109 (2): 195–200. doi:10.1016/j.fertnstert.2017.12.019. ISSN 0015-0282. PMID 29447662.
- ^ Rose, Nancy C.; Kaimal, Anjali J.; Dugoff, Lorraine; Norton, Mary E.; Medicin, American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins-ObstetricsCommittee on GeneticsSociety for Maternal-Fetal (2020). "Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226". Obstetrics & Gynecology. 136 (4): e48–e69. doi:10.1097/AOG.0000000000004084. ISSN 0029-7844. PMID 32804883.
- ^ Skrzypek, Hannah; Hui, Lisa (2017-07-01). "Noninvasive prenatal testing for fetal aneuploidy and single gene disorders". Best Practice & Research Clinical Obstetrics & Gynaecology. 42: 26–38. doi:10.1016/j.bpobgyn.2017.02.007. ISSN 1521-6934. PMID 28342726.
- ^ "What is noninvasive prenatal testing (NIPT) and what disorders can it screen for?: MedlinePlus Genetics". medlineplus.gov. Retrieved 2021-06-27.
- ^ Shamshirsaz, Alireza A.; Benn, Peter; Egan, James F.X. (2010-09-01). "The Role of Second-Trimester Serum Screening in the Post–First-Trimester Screening Era". Clinics in Laboratory Medicine. 30 (3): 667–676. doi:10.1016/j.cll.2010.04.013. ISSN 0272-2712. PMID 20638580.
- ^ a b Allyse, Megan; Minear, Mollie A.; Berson, Elisa; Sridhar, Shilpa; Rote, Margaret; Hung, Anthony; Chandrasekharan, Subhashini (2015-01-16). "Non-invasive prenatal testing: a review of international implementation and challenges". International Journal of Women's Health. 7: 113–126. doi:10.2147/IJWH.S67124. PMC 4303457. PMID 25653560. Retrieved 2021-06-27.
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- ^ Hall, A.; Bostanci, A.; Wright, C. F. (2010). "Non-Invasive Prenatal Diagnosis Using Cell-Free Fetal DNA Technology: Applications and Implications". Public Health Genomics. 13 (4): 246–255. doi:10.1159/000279626. ISSN 1662-4246. PMID 20395693. S2CID 26020661.
- ^ Hung, E. C. W.; Chiu, R. W. K.; Lo, Y. M. D. (2009-04-01). "Detection of circulating fetal nucleic acids: a review of methods and applications". Journal of Clinical Pathology. 62 (4): 308–313. doi:10.1136/jcp.2007.048470. ISSN 0021-9746. PMID 19329710. S2CID 21367768.
- ^ Lo, Y. M. D. (2009). "Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: a review of the current state of the art". BJOG: An International Journal of Obstetrics & Gynaecology. 116 (2): 152–157. doi:10.1111/j.1471-0528.2008.02010.x. ISSN 1471-0528. PMID 19076946. S2CID 6946087.
- ^ Nicolaides, Kypros H.; Syngelaki, Argyro; Ashoor, Ghalia; Birdir, Cahit; Touzet, Gisele (2012-11-01). "Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population". American Journal of Obstetrics & Gynecology. 207 (5): 374.e1–374.e6. doi:10.1016/j.ajog.2012.08.033. ISSN 0002-9378. PMID 23107079.
- ^ Zimmermann, Bernhard; Hill, Matthew; Gemelos, George; Demko, Zachary; Banjevic, Milena; Baner, Johan; Ryan, Allison; Sigurjonsson, Styrmir; Chopra, Nikhil; Dodd, Michael; Levy, Brynn (2012). "Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci". Prenatal Diagnosis. 32 (13): 1233–1241. doi:10.1002/pd.3993. ISSN 1097-0223. PMC 3548605. PMID 23108718.
- ^ Palomaki, Glenn E.; Deciu, Cosmin; Kloza, Edward M.; Lambert-Messerlian, Geralyn M.; Haddow, James E.; Neveux, Louis M.; Ehrich, Mathias; van den Boom, Dirk; Bombard, Allan T.; Grody, Wayne W.; Nelson, Stanley F. (2012). "DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study". Genetics in Medicine. 14 (3): 296–305. doi:10.1038/gim.2011.73. ISSN 1530-0366. PMC 3938175. PMID 22281937.
- ^ Dickens, Bernard M. (2014). "Ethical and legal aspects of noninvasive prenatal genetic diagnosis". International Journal of Gynecology & Obstetrics. 124 (2): 181–184. doi:10.1016/j.ijgo.2013.11.001. ISSN 1879-3479. PMID 24299974. S2CID 29627343.
- ^ Devaney, Stephanie A.; Palomaki, Glenn E.; Scott, Joan A.; Bianchi, Diana W. (2011-08-10). "Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA: A Systematic Review and Meta-analysis". JAMA. 306 (6): 627–636. doi:10.1001/jama.2011.1114. ISSN 0098-7484. PMC 4526182. PMID 21828326.
- ^ Goodspeed, Taylor A.; Allyse, Megan; Sayres, Lauren C.; Norton, Mary E.; Cho, Mildred K. (2013-01-01). "Translating cell-free fetal DNA technology: structural lessons from non-invasive RhD blood typing". Trends in Biotechnology. 31 (1): 7–9. doi:10.1016/j.tibtech.2012.09.001. ISSN 0167-7799. PMC 6309969. PMID 23040170.
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