In early April, a study on NIPS was published in The New England Journal of Medicine[1] (cf. Gènéthique du 7 avril 2015). These results were mostly welcomed by the media. However, the information conveyed confused “screening” with “diagnosis”. This confusion has clouded the understanding of results and the actual issues involved.
The NEXT[2] study concerned investigated the hypothesis that NIPS performs more effectively than “standard screening”, i.e. an evaluation of the risk that a child has Down syndrome by measuring nuchal translucency and maternal serum markers. This screening differs from amniocentesis, which can diagnose Down syndrome.
NIPS is a test for detecting Down syndrome based on an analysis of foetal DNA circulating in the mother’s blood. It was developed in 2008, launched on the market in some countries in 2011 and has been marketed in France by the Cerba laboratory since the autumn of 2013. It has already been the subject of several studies, but mostly involving female populations “at risk”of Down syndrome. The NEXT study will therefore complete results by carrying out the NIPS test in the general population.
This study was financed by the Ariosa Diagnostic laboratory and conducted in 6 different countries.Almost 20,000 pregnant women were enrolled between March 2012 and April 2013.
Every woman underwent standard screening and non-invasive screening. The study concludes that “NIPS studies are more effective than traditional screening during the first trimester to screen for Down syndrome in the general population”, and that the principal advantage of this test is to reduce the number of invasive samples (by amniocentesis).
In fact, in the sample of women tested, NIPS detected 47 women at risk, 38 of whom had a child with Down syndrome compared to standard screening, which detected 884 women at risk including 30 carrying a child with Down syndrome. Following diagnosis by amniocentesis, 38 women were actually found to be carrying a child with Down syndrome. NIPS detected 100% of cases with 0.06% false positives compared to standard screening with a 79% detection rate and 5.4% of false positives.
However, the results do not take into account the 3% of women unable to undergo the NIPS test because the quantity of foetal DNA in the mother’s blood was less than 4% or because of a failed test. In this group, there were 13 cases of aneuploidy [3] including 3 cases of Down syndrome (detected by standard screening). The study concluded that other research should be carried out or an invasive test performed directly in women for whom NIPS testing proved inconclusive (3% of cases in the NEXT study).
Furthermore, NIPS cannot detect the other 30 chromosome anomalies detected with standard screening. It “only” screens for Down Syndrome, Edward’s syndrome and Patau syndrome.
The authors therefore recommended that “caution should be exercised” given the cost of this screening technique. “Although NIPS is more sensitive and specific compared to standard screening, it offers fewer advantages considering the number of cases with ‘no results’”.
As Jean Yves Nau pointed out with regard to this matter, “technical considerations mask the reality of ethical dimensions”. The decisions taken by the CCNE in January 2013 and the CNGOF[4] in April of the same year, focus on the role of these new tests in the care framework. Pending announcements from the DGS[5] or HAS[6] also focus on the economic problems associated with these tests.
The results of the SAFE21 study (during 2016), coordinated by the Necker Hospital and Biomnis Laboratory, are also pending. Once again, the issue focuses solely on the medical-economic impact of NIPS.
But what about the basic question of prenatal screening?
[1] New England Journal of medicine, cell-free DNA Analysis for Non-invasive Examination of Trisomy, Norton & al., 01/04/2015.
[2] Non Invasive Examination of Trisomy.
[3] Anomalie du nombre de chromosomes dans une cellule (Abnormal number of chromosomes in a cell)
[4] Collège National des Gynécologues et Obstétriciens Français (French National College of Gynaecologists and Obstetricians)
[5] Direction Générale de la Santé (French General Health Directorate)
[6] Haute Autorité en Santé (French Health Service)