Skip to main content
SpringerLink
Log in

Current Status of Noninvasive Prenatal Testing and Counselling Considerations: An Indian Perspective

  • Review Article
  • Published:
Journal of Fetal Medicine

Abstract

Uptake of noninvasive prenatal testing (NIPT) is rapidly expanding around the world. Here, we provide an overview of the current global state of NIPT, describe the expansion of the test menu, highlight alternative prenatal test service delivery, and discuss NIPT counseling considerations. We also provide a perspective on utilisation of NIPT in India, which has unique challenges for implementing NIPT given its large population, vast territory, and diverse ethnic groups. The barriers to implementation of NIPT in India are also discussed. Current recommendations regarding use of NIPT made by professional societies vary in different regions and such recommendations for NIPT in India will be helpful to provide general guidance to the health care providers, but will likely require modifications for implementation in India.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350(9076):485–7.

    Article  CAS  PubMed  Google Scholar 

  2. Agarwal A, Sayres LC, Cho MK, Cook-Deegan R, Chandrasekharan S. Commercial landscape of noninvasive prenatal testing in the United States. Prenat Diagn. 2013;33(6):521–31.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chandrasekharan S, Minear MA, Hung A, Allyse M. Noninvasive prenatal testing goes global. Sci Transl Med. 2014;6(231):231fs15.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Allyse M, Minear MA, Berson E, Sridhar S, Rote M, Hung A, et al. Non-invasive prenatal testing: a review of international implementation and challenges. Int J Womens Health. 2015;7:113–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Verma IC, Lall M, Dua Puri R. Down syndrome in India–diagnosis, screening, and prenatal diagnosis. Clin Lab Med. 2012;32(2):231–48.

    Article  PubMed  Google Scholar 

  6. Bianchi DW, Rava RP, Sehnert AJ. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014;371(6):578.

    CAS  PubMed  Google Scholar 

  7. Van Opstal D, van Maarle MC, Lichtenbelt K, Weiss MM, Schuring-Blom H, Bhola SL, et al. Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS: results of the TRIDENT study. Genet Med. 2018;20(5):480–5.

    Article  PubMed  Google Scholar 

  8. Pertile MD, Halks-Miller M, Flowers N, Barbacioru C, Kinnings SL, Vavrek D, et al. Rare autosomal trisomies revealed by maternal plasma DNA sequencing suggest increased risk of feto-placental disease. Sci Transl Med. 2017;9(405):1240.

    Article  CAS  Google Scholar 

  9. Akolekar R, Beta J, Picciarelli G, Ogilvie C, D’Antonio F. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2015;45(1):16–26.

    Article  CAS  PubMed  Google Scholar 

  10. Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015;372(17):1589–97.

    Article  CAS  PubMed  Google Scholar 

  11. Gil MM, Accurti V, Santacruz B, Plana MN, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017;50(3):302–14.

    Article  CAS  PubMed  Google Scholar 

  12. The American College of Obstetricians and Gynecologists, Society for Maternal Fetal Medicine. Practice Bulletin No. 163 Summary: Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127(5):979–81.

  13. Hui L, Barclay J, Poulton A, Hutchinson B, Halliday JL. Prenatal diagnosis and socioeconomic status in the non-invasive prenatal testing era: a population-based study. Aust N Z J Obstet Gynaecol. 2018;58(4):404–10.

    Article  PubMed  Google Scholar 

  14. Human Genetics Society of Australasia/Royal Australian New Zealand College of Obstetrics and Gynaecology. Prenatal screening and diagnosis of chromosomal and genetics conditions in the fetus in pregnancy, 2016 [23 Aug 2019]. https://www.ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Prenatal-screening_1.pdf?ext=.pdf.

  15. van Schendel RV, van El CG, Pajkrt E, Henneman L, Cornel MC. Implementing non-invasive prenatal testing for aneuploidy in a national healthcare system: global challenges and national solutions. BMC Health Serv Res. 2017;17(1):670.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chitty LS, Wright D, Hill M, Verhoef TI, Daley R, Lewis C, et al. Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units. BMJ. 2016;354:i3426.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Engels MA, Heijboer AC, Blankenstein MA, van Vugt JM. Performance of first-trimester combined test for Down syndrome in different maternal age groups: reason for adjustments in screening policy? Prenat Diagn. 2011;31(13):1241–5.

    Article  PubMed  Google Scholar 

  18. Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB, et al. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012;207(2):137.e1–8.

    Article  Google Scholar 

  19. Mazloom AR, Dzakula Z, Oeth P, Wang H, Jensen T, Tynan J, et al. Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma. Prenat Diagn. 2013;33(6):591–7.

    Article  CAS  PubMed  Google Scholar 

  20. Samango-Sprouse C, Banjevic M, Ryan A, Sigurjonsson S, Zimmermann B, Hill M, et al. SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy. Prenat Diagn. 2013;33(7):643–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wellesley D, Dolk H, Boyd PA, Greenlees R, Haeusler M, Nelen V, et al. Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe. Eur J Hum Genet. 2012;20(5):521–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ehrich M, Tynan J, Mazloom A, Almasri E, McCullough R, Boomer T, et al. Genome-wide cfDNA screening: clinical laboratory experience with the first 10,000 cases. Genet Med. 2017;19(12):1332–7.

    Article  PubMed  Google Scholar 

  23. Lau TK, Cheung SW, Lo PS, Pursley AN, Chan MK, Jiang F, et al. Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center. Ultrasound Obstet Gynecol. 2014;43(3):254–64.

    Article  CAS  PubMed  Google Scholar 

  24. Bayindir B, Dehaspe L, Brison N, Brady P, Ardui S, Kammoun M, et al. Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management. Eur J Hum Genet. 2015;23(10):1286–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fiorentino F, Bono S, Pizzuti F, Duca S, Polverari A, Faieta M, et al. The clinical utility of genome-wide non invasive prenatal screening. Prenat Diagn. 2017;37(6):593–601.

    Article  CAS  PubMed  Google Scholar 

  26. Scott F, Bonifacio M, Sandow R, Ellis K, Smet ME, McLennan A. Rare autosomal trisomies: Important and not so rare. Prenat Diagn. 2018;38(10):765–71.

    Article  CAS  PubMed  Google Scholar 

  27. Huang X, Zheng J, Chen M, Zhao Y, Zhang C, Liu L, et al. Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies. Prenat Diagn. 2014;34(4):335–40.

    Article  CAS  PubMed  Google Scholar 

  28. Fosler L, Winters P, Jones KW, Curnow KJ, Sehnert AJ, Bhatt S, et al. Aneuploidy screening by non-invasive prenatal testing in twin pregnancy. Ultrasound Obstet Gynecol. 2017;49(4):470–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gil MM, Galeva S, Jani J, Konstantinidou L, Akolekar R, Plana MN, et al. Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of The Fetal Medicine Foundation results and meta-analysis. Ultrasound Obstet Gynecol. 2019;53(6):734–42.

    CAS  PubMed  Google Scholar 

  30. Liang D, Lin Y, Qiao F, Li H, Wang Y, Zhang J, et al. Perinatal outcomes following cell-free DNA screening in > 32 000 women: Clinical follow-up data from a single tertiary center. Prenat Diagn. 2018;38(10):755–64.

    Article  CAS  PubMed  Google Scholar 

  31. Liang D, Cram DS, Tan H, Linpeng S, Liu Y, Sun H, et al. Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes. Genet Med. 2019. https://doi.org/10.1038/s41436-019-0467-4.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Helgeson J, Wardrop J, Boomer T, Almasri E, Paxton WB, Saldivar JS, et al. Clinical outcome of subchromosomal events detected by whole-genome noninvasive prenatal testing. Prenat Diagn. 2015;35(10):999–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ravi H, McNeill G, Goel S, Meltzer SD, Hunkapiller N, Ryan A, et al. Validation of a SNP-based non-invasive prenatal test to detect the fetal 22q11.2 deletion in maternal plasma samples. PLoS ONE. 2018;13(2):0193476.

    Article  CAS  Google Scholar 

  34. Schmid M, Wang E, Bogard PE, Bevilacqua E, Hacker C, Wang S, et al. Prenatal screening for 22q11.2 deletion using a targeted microarray-based cell-free DNA test. Fetal Diagn Ther. 2017;44:299–304. https://doi.org/10.1159/000484317.

    Article  PubMed  Google Scholar 

  35. Dash P, Puri RD, Kotecha U, Bijarnia S, Lall M, Verma IC. Using noninvasive prenatal testing for aneuploidies in a developing country: lessons learnt. J Fetal Med. 2014;1(3):131–5.

    Article  Google Scholar 

  36. Verma IC, Puri R, Venkataswamy E, Tayal T, Nampoorthiri S, Andrew C, et al. Single nucleotide polymorphism-based noninvasive prenatal testing: experience in India. J Obstet Gynecol India. 2018;68:462–70. https://doi.org/10.1007/s13224-017-1061-9:1-9.

    Article  Google Scholar 

  37. Dar P, Curnow KJ, Gross SJ, Hall MP, Stosic M, Demko Z, et al. Clinical experience and follow-up with large scale single-nucleotide polymorphism-based non-invasive prenatal aneuploidy testing. Am J Obstet Gynecol. 2014;211(5):527.e1–17.

    Article  Google Scholar 

  38. Ashoor G, Syngelaki A, Wagner M, Birdir C, Nicolaides KH. Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012;206(4):322.e1–5.

    Article  CAS  Google Scholar 

  39. Verma IC. Noninvasive prenatal testing: the Indian perspective. J. Fetal Med. 2014;1(3):113–8.

    Article  Google Scholar 

  40. Verma IC, Dua-Puri R, Bijarnia-Mahay S. ACMG 2016 update on noninvasive prenatal testing for fetal aneuploidy: implications for India. J. Fetal Med. 2017;4(1):1–6.

    Article  Google Scholar 

  41. The Pre-natal Diagnostic Techniques (Regulation And Prevention of Misuse) ACT, 1994 (Act No. 57 of 1994). http://chdslsa.gov.in/right_menu/act/pdf/PNDT.pdf.

  42. The Pre-natal Diagnostic Techniques (Regulation and prevention of Misuse) Amendment Act, 2002 (Act No. 14 of 2003). Ministry of Health, Government of India.

  43. The Pre-conception and Prenatal Diagnostic Techniques (Prohibition of Sex Selection) Act 1994, with Amendments Rules (2006). Universal Law Publishing. Lexis Nexis. Gurgaon, Haryana. India.

  44. Bhaktwani A. The PC-PNDT act in a nutshell. Indian J Radiol Imaging. 2012;22(2):133–4.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Dhar M, Payal YS, Krishna V. The Pre-conception and Pre-natal Diagnostic Techniques Act and its implication on advancement of ultrasound in anaesthesiology; time to change mindsets rather than laws. Indian J Anaesth. 2018;62(12):930–3.

    PubMed  PubMed Central  Google Scholar 

  46. Onkar P, Mitra K, Dhok A. Relief from high court against restriction imposed by appropriate authority under PC-PNDT act on number of ultrasound centers visited by a Sonologist. Indian J Radiol Imaging. 2012;22(2):148.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Phadke SR, Puri RD, Ranganath P. Prenatal screening for genetic disorders: suggested guidelines for the Indian Scenario. Indian J Med Res. 2017;146(6):689–99.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Gregg AR, Skotko BG, Benkendorf JL, Monaghan KG, Bajaj K, Best RG, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18(10):1056–65.

    Article  CAS  PubMed  Google Scholar 

  49. Benn P, Borrell A, Chiu RW, Cuckle H, Dugoff L, Faas B, et al. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn. 2015;35(8):725–34.

    Article  PubMed  Google Scholar 

  50. Salomon LJ, Alfirevic Z, Audibert F, Kagan KO, Paladini D, Yeo G, et al. ISUOG updated consensus statement on the impact of cfDNA aneuploidy testing on screening policies and prenatal ultrasound practice. Ultrasound Obstet Gynecol. 2017;49(6):815–6.

    Article  CAS  PubMed  Google Scholar 

  51. van Schendel RV, Page-Christiaens GC, Beulen L, Bilardo CM, de Boer MA, Coumans AB, et al. Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part II-women’s perspectives. Prenat Diagn. 2016;36(12):1091–8.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Abrams DJ, Geier MR. A comparison of patient satisfaction with telehealth and on-site consultations: a pilot study for prenatal genetic counseling. J Genet Couns. 2006;15(3):199–205.

    Article  PubMed  Google Scholar 

  53. Cloutier M, Gallagher L, Goldsmith C, Akiki S, Barrowman N, Morrison S. Group genetic counseling: an alternate service delivery model in a high risk prenatal screening population. Prenat Diagn. 2017;37(11):1112–9.

    Article  PubMed  Google Scholar 

  54. Cuckle H. cfDNA screening performance: accounting for and reducing test failures. Ultrasound Obstet Gynecol. 2017;49(6):689–92.

    Article  CAS  PubMed  Google Scholar 

  55. Yaron Y. The implications of non-invasive prenatal testing failures: a review of an under-discussed phenomenon. Prenat Diagn. 2016;36(5):391–6.

    Article  CAS  PubMed  Google Scholar 

  56. Rava RP, Srinivasan A, Sehnert AJ, Bianchi DW. Circulating fetal cell-free DNA fractions differ in autosomal aneuploidies and monosomy X. Clin Chem. 2014;60(1):243–50.

    Article  CAS  PubMed  Google Scholar 

  57. Hartwig TS, Ambye L, Sorensen S, Jorgensen FS. Discordant non-invasive prenatal testing (NIPT)—a systematic review. Prenat Diagn. 2017;37(6):527–39.

    Article  PubMed  Google Scholar 

  58. Kuppermann M, Pena S, Bishop JT, Nakagawa S, Gregorich SE, Sit A, et al. Effect of enhanced information, values clarification, and removal of financial barriers on use of prenatal genetic testing: a randomized clinical trial. JAMA. 2014;312(12):1210–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Beulen L, van den Berg M, Faas BH, Feenstra I, Hageman M, van Vugt JM, et al. The effect of a decision aid on informed decision-making in the era of non-invasive prenatal testing: a randomised controlled trial. Eur J Hum Genet. 2016;24(10):1409–16.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Hilgart JS, Hayward JA, Coles B, Iredale R. Telegenetics: a systematic review of telemedicine in genetics services. Genet Med. 2012;14(9):765–76.

    Article  PubMed  Google Scholar 

  61. Kaiser AS, Ferris LE, Pastuszak AL, Llewellyn-Thomas H, Johnson JA, Conacher S, et al. The effects of prenatal group genetic counselling on knowledge, anxiety and decisional conflict: issues for nuchal translucency screening. J Obstet Gynaecol. 2002;22(3):246–55.

    Article  PubMed  Google Scholar 

  62. Hunter AG, Cappelli M, Humphreys L, Allanson JE, Chiu TT, Peeters C, et al. A randomized trial comparing alternative approaches to prenatal diagnosis counseling in advanced maternal age patients. Clin Genet. 2005;67(4):303–13.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Kristine Jinnett, Sucheta Bhatt, Christin Coffeen, and Kirsten Curnow (Illumina, Inc.) for their assistance in the preparation of the manuscript.

Author information

Authors and Affiliations

  1. Medical Affairs, Illumina, Inc., 5200 Illumina Way, San Diego, CA, 92122, USA

    James D. Massa

  2. Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, 110060, India

    Veronica Arora, Meenakshi Lallar, Sunita Bijarnia, Ratna Dua Puri & Ishwar C. Verma

Authors
  1. James D. Massa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Veronica Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Meenakshi Lallar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sunita Bijarnia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ratna Dua Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ishwar C. Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to James D. Massa or Ishwar C. Verma.

Ethics declarations

Conflict of interest

JM is an employee of Illumina, Inc. VA, ML, SB, RDP and ICV are employees of Institute of Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Massa, J.D., Arora, V., Lallar, M. et al. Current Status of Noninvasive Prenatal Testing and Counselling Considerations: An Indian Perspective. J. Fetal Med. 7, 9–16 (2020). https://doi.org/10.1007/s40556-019-00228-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40556-019-00228-4

Keywords

Search

Navigation