Performance capabilities of prenatal diagnosis of chromosomal anomalies: what changed with the introduction of non-invasive prenatal test (NIPT)?

Literature review

Authors

DOI:

https://doi.org/10.18370/2309-4117.2021.60.21-30

Keywords:

cell-free fetal DNA fraction (cffDNA), combined first trimester screening, invasive diagnostics, aneuploidy, chromosomal anomalies, trisomy 21, 13, 18, massively parallel sequencing

Abstract

This review systematizes scientific data on the possibilities and limitations of combined prenatal screening for detecting common chromosomal abnormalities (CA) in the first trimester of pregnancy, as well as an innovative technology – non-invasive prenatal test (NIPT) based on free fetal DNA fraction. A review of current clinical guidelines on the place of NIPT in models of prenatal screening, the experience of various countries on the implementation of NIPT in national programs for prenatal screening of CA was carried out. Also, a synthesis of evidence and expert opinions on the controversial issues of the feasibility of using the extended options of NIPT (beyond the identification of common aneuploidies as trisomy 21, 13, 18) was carried out, a review of current data on the possibilities and limitations of various NIPT techniques was carried out.
Despite the general increase in the sensitivity of prenatal screening for CA due to the combination of clinical, biochemical and ultrasound indicators, its main disadvantage is insufficient specificity (the frequency of false positive results of 5%). One of the ways to increase the effectiveness of prenatal screening for CA is the study of free fraction of fetal DNA (NIPT). According to a 2017 meta-analysis, the sensitivity of NIPT is more than 99% for trisomy 21, 98% for trisomy 18, and 99% for trisomy 13 with a specificity of 99%. This high efficacy has been confirmed in subsequent studies, making NIPT the best screening test for the most common trisomies – Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13). NIPT can be used as the first line of prenatal screening or as a second line after combined first trimester screening.
Since 2015, NIPT has been included in the clinical guidelines of international and national professional societies. Common to the 11 reviewed documents is the recognition of NIPT as an important tool for increasing the efficiency of prenatal detection of CA, information about which should be provided to all pregnant women.
In order for the pregnant woman to receive the maximum benefit from NIPT, pre- and post-test counseling with an explanation of the possibilities and limitations of the method in general and in the given clinical situation is crucial.

Author Biographies

O.A. Burka, Bogomolets National Medical University; “DILA” Medical Laboratory, Kyiv

PhD, associate professor at the Obstetrics and Gynaecology Department No. 1;
Scientific consultant

V.S. Cherevashko, “DILA” Medical Laboratory; Specialized medical and genetic center of the National Children’s Specialized Hospital “OKHMATDYT” of the MoH of Ukraine, Kyiv

Scientific consultant

D.A. Martynova, “DILA” Medical Laboratory, Kyiv

Scientific consultant

G.I. Ishchenko, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, Kyiv

PhD, researcher, Department of Prevention and Treatment of Pus-inflammatory Diseases in Obstetrics

O.I. Maksian, Chernivtsi Regional Medical Diagnostic Center, Chernivtsi

Head of the Regional center of Antenatal Care of the Fetus and Medical Genetics

References

  1. World Health Organization, Centers for Disease Control and Prevention. Birth defects surveillance: a manual for programme managers (2020).
  2. Ajao, A.E., Adeoye, I.A. “Prevalence, risk factors and outcome of congenital anomalies among neonatal admissions in OGBOMOSO, Nigeria.” BMC Pediatr 19.1 (2019). DOI: 10.1186/S12887-019-1471-1
  3. Ahmed, A. “Assessment of Risk Factors for Fetal Congenital Anomalies among Pregnant Women at Cairo University Hospitals.” J Am Sci 7.11 (2011).
  4. Cuckle, H., Maymon, R. “Development of prenatal screening – A historical overview.” Semin Perinatol 40.1 (2016): 12–22. DOI: 10.1053/j.semperi.2015.11.003
  5. Corsello, G., Giuffre, M. “Congenital malformations.” J Matern Fetal Neonatal Med 25.1 (2012): 25–9. DOI: 10.3109/14767058.2012.664943
  6. Toufaily, M.N., Westgate, M.H., Lin, A.E., Holmes, L.B. “Causes of Congenital Malformations.” Birth Defects Res 110.2 (2018): 87–91. DOI: 10.1002/bdr2.1105
  7. Henderson, J.T., Thompson, J.H., Burda, B.U., et al. Screening for Preeclampsia. A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 148. Rockville (MD). Agency for Healthcare Research and Quality (US) (2017).
  8. Guerby, P., Bujold, E. “Early Detection and Prevention of Intrauterine Growth Restriction and Its Consequences.” JAMA Pediatr 174.8 (2020): 749–50. DOI: 10.1001/JAMAPEDIATRICS.2020.1106
  9. Leite, D.F.B., Cecatti, J.G. “Fetal Growth Restriction Prediction: How to Move beyond.” Sci World J 2019 (2019). DOI: 10.1155/2019/1519048
  10. Glover, A.V., Manuck, T.A. “Screening for spontaneous preterm birth and resultant therapies to reduce neonatal morbidity and mortality: A review.” Semin Fetal Neonatal Med 23.2 (2018): 126–32. DOI: 10.1016/J.SINY.2017.11.007
  11. Straus, S.E., Glasziou, P., Richardson, W.S., Haynes, R.B. Evidence-based medicine E-book: How to practice and teach EBM. Elsevier Health Sciences (2018).
  12. Trevethan, R. “Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and Pitfalls in Research and Practice.” Front Public Heal (2017). DOI: 10.3389/FPUBH.2017.00307
  13. Wald, N.J. “Guidance on terminology.” JMS 15.1 (2008): 50. DOI: 10.1258/JMS.2008.008GOT
  14. Hassold, T., et al. “Human aneuploidy: Incidence, origin and etiology.” Environmental and Molecular Mutagenesis 28.3 (1996): 167–75. DOI: 10.1002/(SICI)1098-2280(1996)28:3<167::AID-EM2>3.0.CO;2-B
  15. Jobanputra, V., Roy, K.K., Kriplani, A., Kucheria, K. “Prenatal diagnosis of chromosomal abnormalities in women with high risk pregnancies.” Indian J Med Res 114 (2001): 148–55.
  16. Bonomi, M., et al. “Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism.” Journal of Endocrinological Investigation 40.2 (2017): 123–34. DOI: 10.1007/s40618-016-0541-6
  17. Roberts, A.J., Fechner, P.Y. “Description of Turner Syndrome.” In: Turner Syndrome. Springer International Publishing (2020).
  18. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins –Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. “Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226.” Obstet Gynecol 136.4 (2020): 48–69. DOI: 10.1097/AOG.0000000000004084
  19. Antonarakis, S.E., et al. “Down syndrome.” Nat Rev Dis Prim 6.1 (2020): 1–20. DOI: 10.1038/s41572-019-0143-7
  20. Nussbaum, R., McInnes, R.R., Willard, H.F. Thompson & Thompson genetics in medicine e-book. Elsevier Health Sciences (2015).
  21. Flowers, N.J., et al. “Genome-wide noninvasive prenatal screening for carriers of balanced reciprocal translocations.” Genet Med 22.12 (2020): 1944–55. DOI: 10.1038/s41436-020-0930-2
  22. Wright, D., Syngelaki, A., Bradbury, I., et al. “First-Trimester Screening for Trisomies 21, 18 and 13 by Ultrasound and Biochemical Testing.” Fetal Diagn Ther 35.2 (2014): 118–26. DOI: 10.1159/000357430
  23. Nicolaides, K.H. “Screening for fetal aneuploidies at 11 to 13 weeks.” Prenatal diagnosis 31.1 (2011): 7-15. DOI: 10.1002/PD.2637
  24. Kagan, K.O., Staboulidou, I., Cruz, J., et al. “Two-stage first-trimester screening for trisomy 21 by ultrasound assessment and biochemical testing.” Ultrasound Obstet Gynecol 36.5 (2010): 542–7. DOI: 10.1002/UOG.7663
  25. Santorum, M., Wright, D., Syngelaki, A., et al. “Accuracy of first-trimester combined test in screening for trisomies 21, 18 and 13.” Ultrasound in Obstetrics & Gynecology 49.6 (2017): 714–20. DOI: 10.1002/uog.17283
  26. Alldred, S.K., et al. “First trimester ultrasound tests alone or in combination with first trimester serum tests for Down’s syndrome screening.” Cochrane Database Syst Rev 3 (2017). DOI: 10.1002/14651858.CD012600
  27. Bischoff, F.Z., Lewis, D.E., Simpson, J.L. “Cell-free fetal DNA in maternal blood: kinetics, source and structure.” Hum Reprod Update11.1 (2005): 59–67. DOI: 10.1093/HUMUPD/DMH053
  28. Yan, Y.Y., Guo, Q.R., Wang, F.H., et al. “Cell-Free DNA: Hope and Potential Application in Cancer.” Frontiers in Cell and Developmental Biology 9 (2021): 192. DOI: 10.3389/FCELL.2021.639233
  29. Breveglieri, G., D’Aversa, E., Finotti, A., Borgatti, M. “Non-invasive prenatal testing using fetal DNA.” Molecular diagnosis & therapy 23.2 (2019): 291–9. DOI: 10.1007/s40291-019-00385-2
  30. Masuzaki, H. Fetal Morph Functional Diagnosis (2021).
  31. Renga, B. “Noninvasive prenatal diagnosis of fetal aneuploidy using cell free fetal DNA.” European Journal of Obstetrics & Gynecology and Reproductive Biology 225 (2018): 5–8. DOI: 10.1016/j.ejogrb.2018.03.033
  32. Skrzypek, H., Hui, L. “Noninvasive prenatal testing for fetal aneuploidy and single gene disorders.” Best Practice & Research Clinical Obstetrics & Gynaecology 42 (2017): 26–38.
  33. Carbone L., et al. “Non-invasive prenatal testing: Current perspectives and future challenges.” Genes (Basel) 12.1 (2021): 1–12. DOI: 10.3390/genes12010015
  34. Gil, M.M., Accurti, V., Santacruz, B., et al. “Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis.” Ultrasound in Obstetrics & Gynecology 50.3 (2017): 302–14. DOI: 10.1002/uog.17484
  35. Norton, M.E., et al. “Cell-free DNA Analysis for Noninvasive Examination of Trisomy.” The New England Journal of Medicine 372.17 (2015): 1589–97. DOI: 10.1056/NEJMOA1407349
  36. Pergament, E., et al. “Single-Nucleotide Polymorphism-Based Noninvasive Prenatal Screening in a High-Risk and Low-Risk Cohort.” Obstet Gynecol 124.201 (2014): 210. DOI: 10.1097/AOG.0000000000000363
  37. Pertile, M.D., et al. “Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies.” Clin Chem 67.9 (2021): 1210–19. DOI: 10.1093/CLINCHEM/HVAB067
  38. La Verde, M., et al. “Performance of cell-free DNA sequencing-based non-invasive prenatal testing: experience on 36,456 singleton and multiple pregnancies.” BMC Med Genomics 14.1 (2021): 1–11. DOI: 10.1186/s12920-021-00941-y
  39. Eiben, B., et al. “Clinical experience with noninvasive prenatal testing in Germany: Analysis of over 500 high-risk cases for trisomy 21, 18, 13 and monosomy X.” Obstet Gynecol Reports 5.1 (2021): 1–7. DOI: 10.15761/ogr.1000157
  40. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. “SMFM Statement: Clarification of recommendations regarding cell-free DNA aneuploidy screening.” Am J Obstet Gynecol 213.6 (2015): 753–4. DOI: 10.1016/j.ajog.2015.09.077
  41. Gregg, A.R. et al. “Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics.” Genet Med 18.10 (2016): 1056–65. DOI: 10.1038/gim.2016.97
  42. Capriglione, S., et al. “First trimester screening for aneuploidy: may combined test and fetal DNA work together?” J Matern Neonatal Med 2020 (2020). DOI: 10.1080/14767058.2020.1849102
  43. Cotarelo-Pérez, C., et al. “A contingent model for cell-free DNA testing to detect fetal aneuploidy after first trimester combined screening.” Eur J Obstet Gynecol Reprod Biol X 1 (2019): 100002. DOI: 10.1016/J.EUROX.2019.100002
  44. Kagan, K.O., Wright, D., Nicolaides, K.H. “First-trimester contingent screening for trisomies 21, 18 and 13 by fetal nuchal translucency and ductus venosus flow and maternal blood cell-free DNA testing.” Ultrasound Obstet Gynecol 45.1 (2015): 42–7. DOI: 10.1002/UOG.14691
  45. Torres Aguilar, M.R., et al. “Contingent prenatal screening for frequent aneuploidies with cell-free fetal DNA analysis.” Taiwan J Obstet Gynecol 60.4 (2021): 745–51. DOI: 10.1016/j.tjog.2021.05.028
  46. Gil, M.M., Revello, R., Poon, L.C., et al. “Clinical implementation of routine screening for fetal trisomies in the UK NHS: cell-free DNA test contingent on results from first-trimester combined test.” Ultrasound in Obstetrics & Gynecology 47.1 (2016): 45–52. DOI: 10.1002/uog.15783
  47. Palka, C., et al. “Non-invasive prenatal screening: A 20-year experience in Italy.” Eur J Obstet Gynecol Reprod Biol X 3 (2019): 100050. DOI: 10.1016/J.EUROX.2019.100050
  48. Lee, J.Y., et al. “Clinical Practice Guidelines for Prenatal Aneuploidy Screening and Diagnostic Testing from Korean Society of Maternal-Fetal Medicine: (2) Invasive Diagnostic Testing for Fetal Chromosomal Abnormalities.” J Korean Med Sci 36.4 (2021): 1–18. DOI: 10.3346/jkms.2021.36.e26
  49. Palomaki, G.E., et al. “International Society for Prenatal Diagnosis Position Statement: cell free (cf) DNA screening for Down syndrome in multiple pregnancies.” Prenat Diagn (2020). DOI: 10.1002/pd.5832
  50. Rieder, W., White, S., McGillivray, G., Hui, L. “Contemporary prenatal aneuploidy screening practice in Australia: Frequently asked questions in the cell-free DNA era.” Aust New Zeal J Obstet Gynaecol 58.4 (2018): 397–403. DOI: 10.1111/ajo.12834
  51. Kozlowski, P., et al. “DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures.” Ultraschall der Medizin 40.2 (2018): 176–92. DOI: 10.1055/a-0631-8898
  52. Audibert, F., et al. “No. 348-Joint SOGC-CCMG Guideline: Update on Prenatal Screening for Fetal Aneuploidy, Fetal Anomalies, and Adverse Pregnancy Outcomes.” J Obstet Gynaecol Canada 39.9 (2017): 805–17. DOI: 10.1016/j.jogc.2017.01.032
  53. Sieroszewski, P., et al. “Cell-free fetal DNA testing in prenatal diagnosis: Recommendations of the Polish Gynecological Society and the Polish Human Genetics Society.” Eur J Obstet Gynecol Reprod Biol 214 (2017): 190–1. DOI: 10.1016/j.ejogrb.2017.05.009
  54. Belgium Society of Human Genetics prenatal working group. Belgian Guidlines for managing incidental findings detected by NIPT. Available from: [https://www.college-genetics.be/nl/voor-de-professionele/good-practice-et-richtlijnen-voor-beroepsbeoefenaars/richtlijnen.html], last accessed Sep 17, 2021.
  55. Salomon, L.J., et al. “ISUOG updated consensus statement on the impact of cfDNA aneuploidy testing on screening policies and prenatal ultrasound practice.” Ultrasound Obstet Gynecol 49.6 (2017): 815–6. DOI: 10.1002/UOG.17483
  56. Benn, P., et al. “Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis.” Prenat Diagn 35.8 (2015): 725–34. DOI: 10.1002/pd.4608
  57. Gadsbøll, K., et al. “Current use of noninvasive prenatal testing in Europe, Australia and the USA: A graphical presentation.” Acta Obstet Gynecol Scand 99.6 (2020): 722–30. DOI: 10.1111/aogs.13841
  58. K. Van Den Bogaert et al. “Outcome of publicly funded nationwide first-tier noninvasive prenatal screening,” Genet. Med., vol. 23, no. 6, pp. 1137–1142, 2021, doi: 10.1038/s41436-021-01101-4
  59. Scott, F., Bonifacio, M., Sandow, R., et al. “Rare autosomal trisomies: Important and not so rare.” Ultrasound Med Biol 45 (2019): S7–S8. DOI: 10.1016/J.ULTRASMEDBIO.2019.07.436
  60. Olenev, A.S., et al. “Adoption of a non-invasive prenatal test (NIPT) in prenatal screening in Moscow: first results.” Russian Open Medical Journal 10.1 (2021): 110.
  61. Zaami, S., Orrico, A., Signore, F., et al. “Ethical, Legal and Social Issues (ELSI) Associated with Non-Invasive Prenatal Testing: Reflections on the Evolution of Prenatal Diagnosis and Procreative Choices.” Genes 12.2 (2021): 204. DOI: 10.3390/GENES12020204
  62. Cernat, A., De Freitas, C., Majid, U., et al. “Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women’s experiences.” BMC pregnancy and childbirth 19.1 (2019): 1–5.
  63. Feldkamp, M.L., Carey, J.C., Byrne, J.L.B., et al. “Etiology and clinical presentation of birth defects: Population based study.” BMJ 357 (2017): 1–8. DOI: 10.1136/bmj.j2249
  64. Goldwaser, T., Klugman, S. “Cell-free DNA for the detection of fetal aneuploidy.” Fertil Steril 109.2 (2018): 195–200. DOI: 10.1016/J.FERTNSTERT.2017.12.019
  65. Lannoo, L., Lenaerts, L., Van Den Bogaert, K., et al. “Non-invasive prenatal testing suggesting a maternal malignancy: What do we tell the prospective parents in Belgium?” Prenat Diagn (2021). DOI: 10.1002/PD.6031
  66. Grömminger, S., et al. “The influence of low molecular weight heparin medication on plasma DNA in pregnant women.” Prenat Diagn 35.11 (2015): 1155–7. DOI: 10.1002/PD.4668
  67. Monden, C., Pison, G., Smits, J. “Twin Peaks: more twinning in humans than ever before.” Hum Reprod 36.6 (2021): 1666–73. DOI: 10.1093/HUMREP/DEAB029

Downloads

Published

2021-09-24

How to Cite

Burka, O., Cherevashko, V., Martynova, D., Ishchenko, G., Maksian, O., & Knyhnytska, S. (2021). Performance capabilities of prenatal diagnosis of chromosomal anomalies: what changed with the introduction of non-invasive prenatal test (NIPT)? Literature review. REPRODUCTIVE ENDOCRINOLOGY, (60), 21–30. https://doi.org/10.18370/2309-4117.2021.60.21-30

Issue

No. 60 (2021)

Section

Pregnancy and childbirth

License

Copyright (c) 2021 О. А. Бурка, В.С. Черевашко, Д.А. Мартинова, Г.І. Іщенко, О.І. Максіян, C.О. Книгницька

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

    1. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.