Non‐invasive prenatal testing: clinical utility and ethical concerns about recent advances

Joseph Thomas, James Harraway and David Kirchhoffer
Med J Aust 2021; 214 (4): . || doi: 10.5694/mja2.50928
Published online: 15 February 2021

Difficulty in achieving proper informed consent for a complex screening test and the varying phenotypic outcomes leaves pregnant women in a precarious situation when results are abnormal

The combined first trimester screening test for Down syndrome, involving a nuchal translucency scan and biochemistry at 11–13 weeks, improved detection rates to 90% when compared with the sensitivity of screening by age‐related a priori risk of around 30% for a false positive rate of 5%.1 The advent of non‐invasive prenatal testing (NIPT) in 2010 as a screening test for the common trisomies was revolutionary, with sensitivity, specificity and detection rates unmatched by the combined first trimester screening programs. NIPT was found to achieve a detection rate for Down syndrome of 99.7%, with a false positive rate of 0.04%.2 However, some NIPT providers now additionally offer extended panels and low resolution whole genome sequencing (WGS) including sex chromosome aneuploidies, rare autosomal aneuploidies, and subchromosomal deletions, duplications and recurrent microdeletions. This comes at a cost of a higher false positive rate and lower positive predictive value.3 Moreover, the expanded panels and WGS NIPT raise issues of clinical utility and ethical concerns.4,5

  • 1 Mater Health, Brisbane, QLD
  • 2 Sullivan Nicolaides Pathology, Brisbane, QLD
  • 3 Queensland Bioethics Centre, Australian Catholic University, Brisbane, QLD



We thank Sailesh Kumar, Robert Cincotta, Glenn Gardener, Scott Petersen (Mater Centre for Maternal Fetal Medicine, Brisbane) and Larry Bergstrom (Mayo Clinic, United States) for valuable discussions and feedback on the topic.

Competing interests:

No relevant disclosures.

  • 1. Nicolaides KH. Patient‐specific risk for chromosomal defects in the 11–13+6 weeks scan. London: Fetal Medicine Foundation, 2004: pp. 13–14.
  • 2. Gil MM, Accurti V, Santacruz B, et al. Analysis of cell‐free DNA in maternal blood in screening for aneuploidies: updated meta‐analysis. Ultrasound Obstet Gynecol 2017; 50: 302–314.
  • 3. Benn P, Grati FR. Genome‐wide non‐invasive prenatal screening for all cytogenetically visible imbalances. Ultrasound Obstet Gynecol 2018; 51: 429–433.
  • 4. Chitty LS, Hudgins L, Norton ME. Current controversies in prenatal diagnosis 2: cell‐free DNA prenatal screening should be used to identify all chromosome abnormalities. Prenat Diagn 2018; 38: 160–165.
  • 5. 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 N Z J Obstet Gynaecol 2018; 58: 397–403.
  • 6. Hayata K, Hiramatsu Y, Masuyama H, et al. Discrepancy between non‐invasive prenatal genetic testing (NIPT) and amniotic chromosomal test due to placental mosaicism: a case report and literature review. Acta Med Okayama 2017; 71: 181–185.
  • 7. Yu T, Li S, Zhao W, Yu D. [False positive non‐invasive prenatal testing results due to vanishing twins]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019; 36: 327–330.
  • 8. Shaffer BL, Norton ME. Cell‐free DNA screening for aneuploidy and microdeletion syndromes. Obstet Gynecol Clin North Am 2018; 45: 13–26.
  • 9. Pertile MD, Halks‐Miller M, Flowers N, et al. Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto‐placental disease. Sci Transl Med 2017; 9: eaan1240.
  • 10. Shaw J, Scotchman E, Chandler N, Chitty L. Non‐invasive prenatal testing for aneuploidy, copy number variants and single gene disorders. Reproduction 2020; 160: A1–A11.
  • 11. Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Prenatal screening and diagnostic testing for fetal chromosomal and genetic conditions. Sydney: RANZCOG, 2018. (viewed Dec 2020).
  • 12. 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 Childbirth 2019; 19: 27.
  • 13. Werner‐Lin A, McCoyd JLM, Bernhardt BA. Actions and uncertainty: how prenatally diagnosed variants of uncertain significance become actionable. Hastings Cent Rep 2019; 49 Suppl 1: S61–S71.
  • 14. Andermann A, Blancquaert I, Beauchamp S, Dery V. Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years. Bull World Health Organ 2008; 86: 317–319.
  • 15. Brownsworld RW. Testing times ahead: non‐invasive prenatal testing and the kind of community we want to be. Mod Law Rev 2018; 18: 646–672.
  • 16. Ubel PA, Scherr KA, Fagerlin A. Autonomy: what’s shared decision making have to do with it? Am J Bioeth 2018; 18: W11–W12.


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