Advertisement

Journal of Genetic Counseling

, Volume 25, Issue 5, pp 1032–1043 | Cite as

The Integration of Noninvasive Prenatal Screening into the Existing Prenatal Paradigm: a Survey of Current Genetic Counseling Practice

  • Emily Suskin
  • Laura Hercher
  • Kathleen Erskine Aaron
  • Komal Bajaj
Original Research

Abstract

Since its introduction four years ago, noninvasive prenatal screening for fetal aneuploidy (NIPS) has been widely adopted as a screening tool for women at a high risk for fetal aneuploidy. As use expands into the general population, questions arise concerning the integration of NIPS into preexisting screening paradigms. This study aims to examine the use of NIPS in current practice among prenatal counselors, predominantly in the United States, in order to inform strategies for the optimal use of both new and existing screening techniques. We electronically surveyed 208 members of the National Society of Genetic Counselors to ascertain how NIPS is currently being used. Genetic counselors were also queried as to the advantages and disadvantages of offering NIPS to all patients regardless of a priori risk. Results indicate substantial variation in practice regarding which patients are offered NIPS and how counselors have incorporated this technology into existing screening routines. The majority of participants report offering NIPS in conjunction with another method of screening for fetal aneuploidy, indicating that NIPS is being used as an addition rather than as a replacement. These screening methods primarily include nuchal translucency (NT) (45.1 %, n = 78) and first trimester serum screening, with or without an NT (19.7 %, n = 34). Furthermore, the majority report that they would be concerned about losing the clinical value of an NT in a complete transition to NIPS (85.4 %, n = 164). Counselors are evenly split on the merits of expanding the use of NIPS to the general population (con: 55.3 %, n = 105; pro: 44.7 %, n = 85). The lack of consensus suggests that updated practice guidelines might benefit counselors. In addition, respondents emphasized the need to better educate patients and providers about the risks, benefits, and limitations of the test.

Keywords

Noninvasive prenatal screening Non-invasive prenatal testing Cell-free DNA Genetic counseling Prenatal screening Aneuploidy 

Notes

Acknowledgments

This study was completed as part of the first author’s Master of Science degree. The authors wish to thank all those who assisted in the development of the survey, data analysis, and those who participated in the study.

Compliance with Ethical Standards

Conflict Of Interest

Authors Emily Suskin, Laura Hercher, Kathleen Erskine Aaron, and Komal Bajaj declare that they have no conflict of interest.

Human Studies and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Animal Studies

No animal studies were carried out by the authors for this article.

References

  1. Abu-rustum, R. S., Daou, L., & Abu-rustum, S. E. (2010). Role of first-trimester sonography. Journal of Ultrasound in Medicine, 29, 1445–1452.PubMedGoogle Scholar
  2. Allyse, M., Minear, M. A., Berson, E., Sridhar, S., Rote, M., Hung, A., & Chandrasekharan, S. (2015). 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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. American College of Obstetricians and Gynecologists (2012). Noninvasive prenatal testing for fetal aneuploidy. Committee opinion No. 545. Obstetrics & Gynecology, 120, 1532–1534.CrossRefGoogle Scholar
  4. American College of Obstetricians and Gynecologists (2015). Cell-free DNA screening for fetal aneuploidy. Committee Opinion No. 640. Obstetrics & Gynecology. doi: 10.1097/AOG.0000000000001007.Google Scholar
  5. Ashoor, G., Syngelaki, A., Poon, L. C. Y., Rezende, J. C., & Nicolaides, K. H. (2013). Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks’ gestation: relation to maternal and fetal characteristics. Ultrasound in Obstetrics & Gynecology, 41, 26–32. doi: 10.1002/uog.12331.CrossRefGoogle Scholar
  6. Atzei, A., Gajewska, K., Huggon, I. C., Allan, L., & Nicolaides, K. H. (2005). Relationship between nuchal translucency thickness and prevalence of major cardiac defects in fetuses with normal karyotype. Ultrasound in Obstetrics & Gynecology, 26(2), 154–157. doi: 10.1002/uog.1936.CrossRefGoogle Scholar
  7. Begleiter, M. L., & Finley, B. E. (2014). Positive predictive value of cell free DNA analysis. American Journal of Obstetrics and Gynecology, 211(July), 81. doi: 10.1016/j.ajog.2014.01.014.CrossRefPubMedGoogle Scholar
  8. Benn, P., Cuckle, H., & Pergament, E. (2013). Non-invasive prenatal testing for aneuploidy: current status and future prospects. Ultrasound in Obstetrics & Gynecology, 42(1), 15–33. doi: 10.1002/uog.12513.CrossRefGoogle Scholar
  9. Benn, P., Borrell, A., Chiu, R., Cuckle, H., Dugoff, L., Faas, B., & Yaron, Y. (2015a). Position statement from the chromosome abnormality screening committee on behalf of the board of the international society for prenatal diagnosis. Prenatal Diagnosis. doi: 10.1002/pd.4608.Google Scholar
  10. Benn, P., Curnow, K. J., Chapman, S., Michalopoulos, S. N., Hornberger, J., & Rabinowitz, M. (2015b). An economic analysis of cell-free DNA non- invasive prenatal testing in the US general pregnancy population. PloS One, 10(7), 1–12. doi: 10.1371/journal.pone.0132313.CrossRefGoogle Scholar
  11. Bianchi, D. W., Sehnert, A. J., & Rava, R. P. (2012). Genome-wide fetal aneuploidy detection by maternal plasma dna sequencing. Obstetrics & Gynecology, 119(6), 1270–1271. doi: 10.1097/AOG.0b013e318258c419.CrossRefGoogle Scholar
  12. Bianchi, D. W., Parker, R. L., Wentworth, J., Madankumar, R., Saffer, C., Das, A. F., & Sehnert, A. J. (2014). DNA sequencing versus standard prenatal aneuploidy screening. New England Journal of Medicine, 370(9), 799–808. doi: 10.1056/NEJMoa1311037.CrossRefPubMedGoogle Scholar
  13. Chetty, S., Garabedian, M. J., & Norton, M. E. (2013). Uptake of noninvasive prenatal testing (NIPT) in women following positive aneuploidy screening. Prenatal Diagnosis, 33(6), 542–546. doi: 10.1002/pd.4125.CrossRefPubMedGoogle Scholar
  14. Dan, S., Wang, W., Ren, J., Li, Y., Hu, H., Xu, Z., & Zhang, X. (2012). Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11105 pregnancies with mixed risk factors. Prenatal Diagnosis, 32(13), 1225–1232. doi: 10.1002/pd.4002.CrossRefPubMedGoogle Scholar
  15. Dar, P., Curnow, K. J., Gross, S. J., Hall, M. P., Stosic, M., Demko, Z., & Benn, P. (2014). Clinical experience and follow-up with large scale single-nucleotide polymorphism-based non-invasive prenatal aneuploidy testing. American Journal of Obstetrics and Gynecology, 211(5), 527.e1–527.e17. doi: 10.1016/j.ajog.2014.08.006.CrossRefGoogle Scholar
  16. Devers, P. L., Cronister, A., Ormond, K. E., Facio, F., Brasington, C. K., & Flodman, P. (2013). Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the national society of genetic counselors. Journal of Genetic Counseling, 22(3), 291–295. doi: 10.1007/s10897-012-9564-0.CrossRefPubMedGoogle Scholar
  17. Dugoff, L. (2010). First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes. Obstetrics & Gynecology, 115(5), 1052–1061. doi: 10.1097/AOG.0b013e3181da93da.CrossRefGoogle Scholar
  18. Ehrich, M., Deciu, C., Zwiefelhofer, T., Tynan, J. A., Cagasan, L., Tim, R., & van den Boom, D. (2011). Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. American Journal of Obstetrics and Gynecology, 204(3), 205.e1–205.e11. doi: 10.1016/j.ajog.2010.12.060.CrossRefGoogle Scholar
  19. Estreich, G. (2014). Consumer-directed advertising for noninvasive prenatal screening. Presented at the NSGC Annual Education Conference, New Orleans.Google Scholar
  20. Fairbrother, G., Burigo, J., Sharon, T., Song, K., Fairbrother, G., Burigo, J., & Song, K. (2015). Prenatal screening for fetal aneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis. Journal of Maternal-Fetal and Neonatal Medicine, 7058(May), 1–5. doi: 10.3109/14767058.2015.1038703.Google Scholar
  21. First trimester screen | Fβ. (2015). Retrieved from http://ntdlabs.com/maternal-marker-testing/first_trimester_screen.php.
  22. Freelon, D. (2013). ReCal OIR: Ordinal, interval, and ratio intercoder reliability as a web service. International Journal of Internet Science, 8(1), 10–16.Google Scholar
  23. Gagnon, A., Wilson, R.D., Audibert, F., Allen, V.M., Blight, C., Brock, J.A., Désilets, V.A., Johnson, J.A., Langlois, S., Summers, A., & Wyatt, P. (2008). Obstetrical complications associated with abnormal maternal serum markers analytes. Journal of Obstetrics and Gynaecology Canada, 30(10), 918–949.Google Scholar
  24. Gil, M. M., Quezada, M. S., Bregant, B., Ferraro, M., & Nicolaides, K. H. (2013). Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies. Ultrasound in Obstetrics & Gynecology, 42(April), 34–40. doi: 10.1002/uog.12504.CrossRefGoogle Scholar
  25. Grati, F. R., Malvestiti, F., Ferreira, J. C. P. B., Bajaj, K., Gaetani, E., Agrati, C., & Simoni, G. (2014). Fetoplacental mosaicism: potential implications for false-positive and false-negative noninvasive prenatal screening results. Genetics in Medicine, 16(8), 620–624. doi: 10.1038/gim.2014.3.CrossRefPubMedGoogle Scholar
  26. Gregg, A. R., Gross, S. J., Best, R. G., Monaghan, K. G., Bajaj, K., Skotko, B. G., & Watson, M. S. (2013). ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genetics in Medicine, 15(5), 395–398. doi: 10.1038/gim.2013.29.CrossRefPubMedGoogle Scholar
  27. Horsting, J. M. H., Dlouhy, S. R., Hanson, K., Quaid, K., Bai, S., & Hines, K. A. (2014). Genetic counselors’ experience with cell-free fetal DNA testing as a prenatal screening option for aneuploidy. Journal of Genetic Counseling, 23(3), 377–400. doi: 10.1007/s10897-013-9673-4.CrossRefPubMedGoogle Scholar
  28. Kaimal, A. J., Norton, M. E., & Kuppermann, M. (2015). Prenatal testing in the genomic age clinical outcomes, quality of life, and costs. Obstetrics & Gynecology, 126(4), 737–746. doi: 10.1097/AOG.0000000000001029.CrossRefGoogle Scholar
  29. Karow, J. (2014). Clinicians discuss NIPT vs invasive diagnostics, ethical issues at prenatal molecular dx conference. Retrieved from https://www.genomeweb.com/molecular-diagnostics/clinicians-discuss-nipt-vs-invasive-diagnostics-ethical-issues-prenatal.
  30. Langlois, S., Brock, J. A, Wilson, R. D., Audibert, F., Carroll, J., Cartier, L., Senikas, V. (2013). Current status in non-invasive prenatal detection of down syndrome, trisomy 18, and trisomy 13 using cell-free DNA in maternal plasma. Journal of Obstetrics and Gynaecology Canada, 35(2), 177–181.Google Scholar
  31. Larion, S., Warsof, S.L., Romary, L., Mlynarczyk, M., Peleg, D., Abuhamad, A.Z. (2014, March-April). Presented at the annual convention of the American Institute of Ultrasound in Medicine, Las Vegas.Google Scholar
  32. Lee, W., Yagel, S., Cohen, S. M., Benacerraf, B. R., Cuckle, H., Kagan, K. O., & Wapner, R. (2015). Noninvasive Prenatal Testing and Fetal Sonographic Screening: Roundtable Discussion. Journal of Ultrasound in Medicine, 34(3), 363–369. doi: 10.7863/ultra.34.3.363.CrossRefPubMedGoogle Scholar
  33. Lo, Y. M., Corbetta, N., Chamberlain, P. F., Rai, V., Sargent I. L., Redman C. W., et al. (1997). Presence of fetal DNA in maternal plasma and serum. Lancet, 350, 485–487.Google Scholar
  34. Malone, F. D., Canick, J. A., Ball, R. H., Nyberg, D. A., Comstock, C. H., Bukowski, R., et al. (2005). First-trimester or second-trimester screening, or both, for Down’s syndrome. New England Journal of Medicine, 353(19), 2001–2011. doi: 10.1056/NEJMoa1404304.CrossRefPubMedGoogle Scholar
  35. Mennuti, M. T., Cherry, A. M., Morrissette, J. J. D., & Dugoff, L. (2013). Is it time to sound an alarm about false-positive cell-free DNA testing for fetal aneuploidy? American Journal of Obstetrics and Gynecology, 209(5), 415–419. doi: 10.1016/j.ajog.2013.03.027.CrossRefPubMedGoogle Scholar
  36. Mennuti, M. T., Dugoff, L., Morrissette, J. J. D., & Cherry, A. M. (2014). Reply. American Journal of Obstetrics and Gynecology, 211(July), 81. doi: 10.1016/j.ajog.2014.01.015.
  37. National Society of Genetic Counselors (2015). NIPT/cfDNA calculator. Retrieved from https://secure.itswebs.com/nsgc/niptcalculator/index.html.
  38. National Society of Genetic Counselors Prenatal Special Interest Group. (2015a). Abnormal prenatal cell-free DNA screening results. Retrieved from http://nsgc.org/page/abnormal-non-invasive-prenatal-testing-results.
  39. National Society of Genetic Counselors Prenatal Special Interest Group. (2015b). Prenatal cell-free DNA screening. Retrieved from http://nsgc.org/page/non-invasive-prenatal-testing-healthcare-providers.
  40. Nicolaides, K. H. (2004). Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. American Journal of Obstetrics and Gynecology, 191(1), 45–67. doi: 10.1016/j.ajog.2004.03.090.CrossRefPubMedGoogle Scholar
  41. Nicolaides, K. H. (2011). Turning the pyramid of prenatal care. Fetal Diagnosis and Therapy, 29(3), 183–196. doi: 10.1159/000324320.CrossRefPubMedGoogle Scholar
  42. Nicolaides, K. H., Syngelaki, A., Ashoor, G., Birdir, C., & Touzet, G. (2012). Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. American Journal of Obstetrics and Gynecology, 207(5), 374.e1–374.e6. doi: 10.1016/j.ajog.2012.08.033.CrossRefGoogle Scholar
  43. Nicolaides, K. H., Wright, D., Poon, L. C., Syngelaki, A., & Gil, M. M. (2013a). First-Trimester Contingent Screening for Trisomy 21 by Biomarkers and Maternal Blood Cell-Free DNA Testing. Ultrasound in Obstetrics & Gynecology, 42(1), 41–50. doi: 10.1002/uog.12511.CrossRefGoogle Scholar
  44. Nicolaides, K. H., Syngelaki, A., Gil, M., Atanasova, V., & Markova, D. (2013b). Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenatal Diagnosis, 33, 575–579. doi: 10.1002/pd.4103.CrossRefPubMedGoogle Scholar
  45. Norton, M. E., Brar, H., Weiss, J., Karimi, A., Laurent, L. C., Caughey, A. B., & Song, K. (2012). Non-Invasive Chromosomal Evaluation (NICE) Study: Results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. American Journal of Obstetrics and Gynecology, 207(2), 137.e1–137.e8. doi: 10.1016/j.ajog.2012.05.021.CrossRefGoogle Scholar
  46. Norton, M. E., Jelliffe-Pawlowski, L. L., & Currier, R. J. (2014). Chromosome abnormalities detected by current prenatal screening and noninvasive prenatal testing. Obstetrics & Gynecology, 124, 979–986. doi: 10.1097/AOG.0000000000000452.CrossRefGoogle Scholar
  47. Norton, M. E., Jacobsson, B., Swamy, G. K., Laurent, L. C., Ranzini, A. C., Brar, H., et al. (2015). Cell-free DNA analysis for noninvasive examination of trisomy. New England Journal of Medicine, 372(17), 1589–1597. doi: 10.1056/NEJMoa1407349.CrossRefPubMedGoogle Scholar
  48. Palomaki, G. E., Kloza, E. M., Lambert-Messerlian, G. M., Haddow, J. E., Neveux, L. M., Ehrich, M., et al. (2011). DNA sequencing of maternal plasma to detect down syndrome: an international clinical validation study. Genetics in Medicine, 13(11), 913–920. doi: 10.1097/GIM.0b013e3182368a0e.CrossRefPubMedGoogle Scholar
  49. Patton, M. Q. (2001). Qualitative evaluation and research methods. Thousand Oaks: Sage.Google Scholar
  50. Pergament, E., Cuckle, H., Zimmermann, B., Banjevic, M., Sigurjonsson, S., Ryan, A., …Rabinowitz, M. (2014). Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstetrics & Gynecology, 124(2 Pt 1), 210–218. doi: 10.1097/AOG.0000000000000363.
  51. Prenatal screening and diagnosis of neural tube defects, Down syndrome, and trisomy 18. (2015). Retrieved from https://www.labcorp.com/wps/wcm/connect/intgeneticslib/IntegratedGenetics/Resources/PDFs/Brochures/maternal-serum-screening-physician-brochure.
  52. Quad screen | Fβ. (2015). Retrieved from http://ntdlabs.com/maternal-marker-testing/quad_screen.php.
  53. Resta, R. (2014). NIPS SPIN [Blog post]. Retrieved from http://thednaexchange.com/2014/04/21/nips-spin/.
  54. Royal Australian and New Zealand College of Obstetricians and Gynaecologists (2015). DNA-based noninvasive prenatal testing for fetal aneuploidy. Retrieved from https://www.ranzcog.edu.au/womens-health/college-communiques/1357-dna-based-noninvasive-prenatal-testing-for-fetal-aneuploidy.html.
  55. Salomon, L. J., Alfirevic, Z., Bilardo, C. M., Chalouhi, G. E., Ghi, T., Kagan, K. O., & Yeo, G. (2013). ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan. Ultrasound in Obstetrics & Gynecology, 41(1), 102–113. doi: 10.1002/uog.12342.CrossRefGoogle Scholar
  56. Shulman, L. (2014). The science of pregnancy management: moving beyond NIPT and through the continuum of care. Presented at the ACMG Annual Clinical Genetics Meeting, Nashville.Google Scholar
  57. Society for Maternal-Fetal Medicine (2015). Prenatal aneuploidy screening using cell-free DNA. SMFM Consult Series #36. American Journal of Obstetrics and Gynecology, 212(6), 711–716. doi: 10.1016/j.ajog.2015.03.043.CrossRefGoogle Scholar
  58. Stoll, K. (2013a). NIPS and the threat to informed decision making [Blog post]. Retrieved from http://thednaexchange.com/2013/11/04/nips-and-the-threat-to-informed-decision-making/.
  59. Stoll, K. (2013b). NIPS is not diagnostic – convincing our patients and convincing ourselves [Blog post]. Retrieved from http://thednaexchange.com/2013/07/11/guest-post-nips-is-not-diagnostic-convincing-our-patients-and-convincing-ourselves/.
  60. Stoll, K. (2014a). Non-invasive prenatal screening: data, marketing, and women’s choices. presented at the NSGC Annual Education conference, New Orleans.Google Scholar
  61. Stoll, K. (2014b). NIPS: microdeletions, macro questions [Blog post]. Retrieved from http://thednaexchange.com/2014/11/02/guest-post-nips-microdeletions-macro-questions/.
  62. Stoll, K., & Lindh, H. (2015). The DNA exchange guest post : PPV puffery? Sizing up NIPT statistics [Blog post]. Retrieved from http://thednaexchange.com/2015/05/04/guest-post-ppv-puffery-sizing-up-nipt-statistics/.
  63. Suskin Kaplan, B., Neto, N., Dar, P., Dolan, S. M., & Klugman, S. (2014). The value of the “double positive” first trimester screen. Nashville: Poster presented at the ACMG Annual Clinical Genetics Meeting.Google Scholar
  64. Syngelaki, A., Chelemen, T., Dagklis, T., Allan, L., & Nicolaides, K. H. (2011). Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11-13 Weeks. Prenatal Diagnosis, 31, 90–102. doi: 10.1002/pd.2642.CrossRefPubMedGoogle Scholar
  65. Tamminga, S., van Schendel, R. V., Rommers, W., Bilardo, C. M., Pajkrt, E., Dondorp, W. J., van Maarle, M., Cornel, M. C., & Henneman, L. (2015). Changing to NIPT as a first-tier screening test and future perspectives: opinions of health professionals. Prenatal Diagnosis. doi: 10.1002/pd.4697.PubMedGoogle Scholar
  66. Walker, B. S., Nelson, R. E., Jackson, B. R., Grenache, D. G., Ashwood, R., & Schmidt, R. L. (2015). A Cost-effectiveness analysis of first trimester non-invasive prenatal screening for fetal trisomies in the united states. PloS One, 1–20. doi: 10.1371/journal.pone.0131402.
  67. Wilson, K. L., Czerwinski, J. L., Hoskovec, J. M., Noblin, S. J., Sullivan, C. M., Harbison, A., et al. (2013). NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy. Journal of Genetic Counseling, 22(1), 4–15. doi: 10.1007/s10897-012-9545-3.CrossRefPubMedGoogle Scholar
  68. Zhang, H., Gao, Y., Jiang, F., Fu, M., Yuan, Y., Guo, Y., & Wang, W. (2015). Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146,958 pregnancies. Ultrasound in Obstetrics & Gynecology, 45(5), 530–538. doi: 10.1002/uog.14792.CrossRefGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2016

Authors and Affiliations

  • Emily Suskin
    • 1
  • Laura Hercher
    • 2
  • Kathleen Erskine Aaron
    • 1
  • Komal Bajaj
    • 1
    • 3
  1. 1.Department of Obstetrics & Gynecology and Women’s HealthAlbert Einstein College of Medicine and Montefiore Medical CenterNew YorkUSA
  2. 2.The Joan H. Marks Graduate Program in Human GeneticsSarah Lawrence CollegeBronxvilleUSA
  3. 3.Jacobi Medical CenterNew York City Health + HospitalsNew YorkUSA

Personalised recommendations