The so called “Next Generation Prenatal Diagnosis” (NGPD)

In the last 30 years, invasive prenatal diagnosis has predominantly involved research into chromosomal anomalies, in particular Down’s Syndrome (1).

In the last 10 years, parents have been requesting ever more information during pregnancy (2-3) and there has been an increase in the number of cases with ultrasound markers concerning possible fetal complications of unknown origin. This has led to the introduction of prenatal diagnosis and increasingly detailed techniques such as CGH Array (4-6).

These techniques have become standard diagnostic practice in cases where the ultrasound scan provides a conflicting result. However, in reality, such procedures are thought to cover only 10% of the fetal anomalies linked to genetic malformations discovered at birth (7).

Prenatal diagnosis is becoming more and more detailed due to the continual legal action taken by parents regarding diagnostic ultrasound which fails to identify fetal anomalies and regarding unwanted births in general (8-10).

In fact, the continuous evolution of human genetics has led to the development of extremely detailed methodologies, which are able to evaluate not only the errors in chromosomes, both “big errors” (karyotype) and “small errors” (microdeletions, microduplications), but also gene mutations.

To date, approximately 19,000 coding genes contained in the human exome have been identified. The recent introduction of NGS (next generation sequencing) has made it possible, in theory, to explore the entire exome and reveal every form of mutation (11-15).

Therefore, it is possible, today, to open up a completely new diagnostic scenario which would have been considered impossible only a few years ago. However, if this development is not controlled, it could lead to a so-called genetic “deviation”, i.e. a genetics that could have unforeseen repercussions on the life and dignity of the individual.

In fact, the risks concerning possible social, emotional and financial consequences in the family and individual is very high. The potential negative impact of prenatal genetic testing must respect the “right not to know”. The exaggeration in ever more detailed testing concerning the genetic structure of the embryo creates tension within a family. In the future, this could create genetic discrimination regarding employment or health insurance costs (16-17).

Despite the fact there is theoretically no technical limit to these methodologies, it is important to establish ethical and moral guidelines, at least regarding how these new methodologies are used in prenatal diagnosis.


  1. Abu-Rustum RS, Daou L, Abu-Rustum SE. Role of first-trimester sonography in the diagnosis of aneuploidy and structural fetal anomalies. J Ultrasound Med. 2010 Oct;29(10):1445-52.
  2. Renna MD, Pisani P, Conversano F, Perrone E, Casciaro E, Renzo GC, Paola MD, Perrone A, Casciaro S. Sonographic markers for early diagnosis of fetal malformations. World J Radiol. 2013 Oct 28;5(10):356-371.
  3. Chasen ST, Razavi AS. Echogenic intracardiac foci: disclosure and the rate of amniocentesis in low-risk patients. Am J Obstet Gynecol. 2013 Oct;209(4):377.
  4. Cheung SW, Shaw CA, Yu W, Li J, Ou Z, Patel A, Yatsenko SA, Cooper ML, Furman P, Stankiewicz P, Lupski JR, Chinault AC, Beaudet AL. Development and validation of a CGH microarray for clinical cytogenetic diagnosis. Genet Med. 2005 Jul-Aug;7(6):422-32.
  5. Cignini P, Dugo N, Giorlandino C, Gauci R, Spata A, Capriglione S, Cafà EV. Prenatal diagnosis of a fetus with a ring chromosome 20 characterized by array-CGH. J Prenat Med. 2012 Oct;6(4):72-3.
  6. Cignini P, Dinatale A, D’Emidio L, Giacobbe A, Pappalardo EM, Ermito S, Bizzoco D, Di Giacomo G, Gabrielli I, Mesoraca A, Giorlandino M, Giorlandino C. Prenatal Diagnosis of a Fetus with de novo Supernumerary Ring Chromosome 16 Characterized by Array Comparative Genomic Hybridization. AJP Rep. 2011 Sep;1(1):29-32. doi: 10.1055/s-0031-1274512. Epub 2011 Mar 18.
  7. Carss KJ, Hillman SC, Parthiban V, McMullan DJ, Maher ER, Kilby MD, Hurles ME. Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound. Hum Mol Genet. 2014 Feb 11.
  8. Frati P, Gulino M, Turillazzi E, Zaami S, Fineschi V. The physician’s breach of the duty to inform the parent of deformities and abnormalities in the foetus: “wrongful Life” actions, a new frontier of medical responsibility. J Matern Fetal Neonatal Med. 2013 Oct 31.
  9. Devisch I. The tribunal of modern life: the case of UZ Brussels in the light of Odo Marquard’s discussion on autonomy and theodicy. J Eval Clin Pract. 2013 Jun;19(3):471-7. doi: 10.1111/jep.12042.
  10. Manaouil C1, Gignon M, Jardé O. 10 years of controversy, twists and turns in the Perruche wrongful life claim: compensation for children born with a disability in France. Med Law. 2012 Dec;31(4):661-9.
  11. Voelkerding KV, Dames SA, Durtschi JD. Next-generation sequencing: from basic research to diagnostics. Clin Chem. 2009 Apr;55(4):641-58. doi: 10.1373/clinchem.2008.112789. Epub 2009 Feb 26. Review.
  12. Jones D, Fiozzo F, Waters B, McKnight D, Brown S. First trimester diagnosis of Meckel-Gruber Syndrome by fetal ultrasound, with molecular identification of CC2D2A mutations by Next-Generation Sequencing. Ultrasound Obstet Gynecol. 2014 Apr 4. doi: 10.1002/uog.13381.
  13. Łaczmańska I1, Stembalska A. New molecular methods in prenatal invasive diagnostics. Ginekol Pol. 2013 Oct;84(10):871-6.
  14. Ansorge WJ. Next-generation DNA sequencing techniques. N Biotechnol. 2009 Apr;25(4):195-203. Epub 2009 Feb 3.
  15. Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008 Oct;26(10):1135g45.
  16. Andorno R. The right not to know: an autonomy-based approach. Journal of Medical Ethics. 2004, 30(5): 435–439
  17. Harmon A. Insurance Fears Lead Many to Shun DNA Tests. The New York Times, February 24, 2008