New DNA antenatal screening for Down's syndrome shown to be a 'transformational advance'

November 8, 2017, Queen Mary, University of London
Credit: CC0 Public Domain

Medical scientists at Queen Mary University of London (QMUL) have demonstrated for the first time that it is possible to incorporate DNA analysis into antenatal screening for three serious chromosome disorders, including Down's syndrome, in a way that is far more accurate than existing methods, and safer and less stressful for mothers.

The new method, called antenatal "reflex DNA screening", which screens for Down's syndrome, Edwards syndrome and Patau syndrome, detected more affected pregnancies than the it replaced, with far fewer false-positives. Reflex DNA screening combines conventional screening with new DNA testing.

The method was implemented in five UK NHS maternity units, screening over 22,000 women between April 2015 and August 2016, and continues to be in use. The findings are published in the journal Genetics in Medicine.

At present, women are offered screening for these three chromosome disorders at 10-14 weeks of pregnancy. The test combines an ultrasound scan and a blood test, and if it shows that a woman is at an increased risk of having an affected pregnancy, she is offered a diagnostic test, an amniocentesis or chorionic villus sampling (CVS); these are invasive tests that involve inserting a needle through the mother's abdomen into her womb to collect samples of fluid surrounding the foetus or tissue from the placenta.

With the new method, women provided a blood sample at about 11 weeks of pregnancy. The sample was divided into two; one used for the conventional screening test and one held in reserve. The first sample was used to assess the women's risk of any of the three disorders. If, on the basis of that test, the risk of having an affected pregnancy was 1 in 800 or a higher risk, the other blood sample was automatically retrieved for a DNA test (i.e. performed in a "reflex" manner), without having to recall the women to provide a fresh blood sample. This avoided needlessly worrying the women by informing them that the DNA test was required because of their increased risk of an affected pregnancy.

Of the 22,812 women screened, 11 per cent had a reflex DNA test. It detected 101 out of the 106 pregnancies affected with one of the three disorders, with only four false-positives, yielding a 95 per cent detection rate (compared with 81 per cent using the existing conventional test alone), and a 0.02 per cent false-positive rate (100-fold reduction in false positives from 2.42 per cent for the combined test). Among pregnancies that tested positive and where the women were offered an invasive diagnostic test, 25 out of 26 were affected by one of the syndromes.

Professor Sir Nicholas Wald, from QMUL's Wolfson Institute of Preventive Medicine, who led the project, said: "The reflex DNA approach has substantial benefits to the well-being of the women screened. Not only are more affected pregnancies identified, but many fewer women will be made acutely anxious by being notified that they have a positive screening result, and among those women with a positive DNA screening result, almost all will have an affected . Reflex screening is also safer than conventional screening as it avoids nearly all invasive diagnostic tests in unaffected pregnancies and miscarriages related to these procedures.

"The reflex DNA approach has beneficial resource implications by reducing the number of women who need counselling on account of a positive screening result, and by avoiding about five out of six diagnostic amniocenteses that would otherwise be indicated. The extra costs of the DNA tests are offset against savings from fewer amniocenteses and associated counselling. The overall balance of costs and savings can be chosen by adjusting the proportion of women who have a reflex DNA test."

He continued: "The National Screening Committee is considering a similar proposal, which involves recalling with a positive initial result for a DNA test, some of whom will be sufficiently anxious to request a diagnostic amniocentesis rather than the DNA test. The reflex method avoids causing worry to this group, and avoids the dilemma in choosing between a DNA screening test and a diagnostic amniocentesis."

Mr Joseph Aquilina, consultant obstetrician at Barts Health NHS Trust who participated in the project, said: "The new reflex DNA approach is transformational. Not only is the screening method better than current practice, but I have more time to devote to other clinical needs, as do the nursing and midwifery staff involved."

The researchers are now approaching other hospitals in the UK to see if they would be interested in adopting the new test. In addition, they say that the test could be adopted by hospitals worldwide so long as they have access to labs that can perform the DNA analysis. "Ideally, the DNA testing would be performed in the existing laboratory in order for the testing process to be seamless," said Professor Wald.

Explore further: Changes to prenatal screening for Down syndrome suggested

More information: Nicholas J Wald, Wayne J Huttly, Jonathan P Bestwick, Robert Old, Joan K Morris, Ray Cheng, Joe Aquilina, Elisabeth Peregrine, Devender Roberts, Zarko Alfirevic. "Prenatal reflex DNA screening for trisomy 21, 18, and 13". Genetics in Medicine. DOI: 10.1038/GIM.2017.188

Related Stories

Changes to prenatal screening for Down syndrome suggested

December 5, 2013
Western Australian researchers say the inclusion of non-invasive prenatal testing (NIPT) into the current Down syndrome screening program would increase detection rates, reduce invasive diagnostic testing and as a result ...

DNA test for Down's syndrome on the NHS could save lives

October 26, 2015
Offering pregnant women a DNA test for Down's syndrome on the NHS would reduce the dependency on invasive tests and potentially save the lives of unborn babies, a study shows.

Study shows that new DNA test to identify Down syndrome in pregnancy is ready for clinical use

October 17, 2011
A new DNA-based prenatal blood test that can strikingly reduce the number of risky diagnostic procedures needed to identify a pregnancy with Down syndrome is ready to be introduced into clinical practice. The test can be ...

Blood test trumps accuracy of standard screening in detecting Down syndrome in early pregnancy

April 1, 2015
A blood test undertaken between 10 to 14 weeks of pregnancy may be more effective in diagnosing Down syndrome and two other less common chromosomal abnormalities than standard non-invasive screening techniques, according ...

Non-invasive first trimester blood test reliably detects Down's syndrome

June 7, 2013
New research has found that routine screening using a non-invasive test that analyzes fetal DNA in a pregnant woman's blood can accurately detect Down's syndrome and other genetic fetal abnormalities in the first trimester. ...

Study finds NIPT detects more than 80 percent of chromosomal abnormalities

February 3, 2014
In a study to be presented on Feb. 6 at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting, in New Orleans, researchers will report that noninvasive prenatal testing detected 83.2 percent of chromosomal ...

Recommended for you

Add broken DNA repair to the list of inherited colorectal cancer risk factors

February 23, 2018
An analysis of nearly 3,800 colorectal cancer patients—the largest germline risk study for this cancer to date—reveals opportunities for improved risk screening and, possibly, treatment.

Team identifies genetic defect that may cause rare movement disorder

February 22, 2018
A Massachusetts General Hospital (MGH)-led research team has found that a defect in transcription of the TAF1 gene may be the cause of X-linked dystonia parkinsonism (XDP), a rare and severe neurodegenerative disease. The ...

Defects on regulators of disease-causing proteins can cause neurological disease

February 22, 2018
When the protein Ataxin1 accumulates in neurons it causes a neurological condition called spinocerebellar ataxia type 1 (SCA1), a disease characterized by progressive problems with balance. Ataxin1 accumulates because of ...

15 new genes identified that shape human faces

February 20, 2018
Researchers from KU Leuven (Belgium) and the universities of Pittsburgh, Stanford, and Penn State have identified 15 genes that determine facial features. The findings were published in Nature Genetics.

New algorithm can pinpoint mutations favored by natural selection in large sections of the human genome

February 20, 2018
A team of scientists has developed an algorithm that can accurately pinpoint, in large regions of the human genome, mutations favored by natural selection. The finding provides deeper insight into how evolution works, and ...

New software helps detect adaptive genetic mutations

February 20, 2018
Researchers from Brown University have developed a new method for sifting through genomic data in search of genetic variants that have helped populations adapt to their environments. The technique, dubbed SWIF(r), could be ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.