New blood test for Down’s syndrome?

Monday March 7 2011

The Daily Mirror reported today that a “blood test for Down's syndrome could spare mums risky invasive examinations”. It went on to describe how researchers have used a new technique to spot DNA differences in foetuses.

The research trialled a new, non-invasive method for detecting Down's syndrome pregnancies. The study used blood samples from 40 women between 11 and 14 weeks into their pregnancy in a blinded test. The test correctly identified all 14 Down’s pregnancies in this group and correctly ruled out the condition in all 26 normal pregnancies.

Currently, Down’s syndrome is diagnosed prenatally using invasive methods such as amniocentesis and chorionic villus sampling. These procedures are not entirely without risk, and in about 1 in 100 women can result in a miscarriage.

This is the latest in a number of studies looking at the feasibility of diagnosing this and other genetic disorders from a maternal blood test. Although the techniques described show promise, further research involving a large-scale study will be required to assess which diagnostic method is the most accurate and reliable, and whether the new tests perform well enough to replace current methods. 

Where did the story come from?

The study was carried out by researchers from the Cyprus Institute of Neurology and Genetics, the University of Cyprus, Mitera Hospital Greece, the National and Kapodistrian University of Athens and the Wellcome Trust Sanger Institute in the UK. The authors report that they were supported by a number of organisations including the Wellcome Trust in the UK. The paper also lists that the authors have declared competing financial interests, details of which can be found online at Nature Medicine . These details were not available at the time of publication. The study was published in the peer-reviewed journal Nature Medicine .

The study was reported accurately by the papers.

What kind of research was this?

The aim of this laboratory study was to test the accuracy of a new genetic technique for detecting Down’s syndrome, using blood samples from 80 pregnant women whose foetuses had already been confirmed as having Down’s or not through other methods.

The authors point out that Down’s is considered to be the most frequent cause of mental retardation, with 1 in 700 newborn babies affected. Currently, it can only be diagnosed through obtaining foetal genetic material through invasive tests such as amniocentesis and chorionic villus sampling. These procedures are not entirely without risk, and in about 1 in 100 women can result in a miscarriage.

The researchers say that research has found that a small amount of DNA from the foetus circulates in the mother’s bloodstream during pregnancy. This is called free foetal DNA (ffDNA). This has given rise to research into potential non-invasive methods of detecting Down’s and other genetic diseases using a maternal blood test.

The theory behind this research is based on the fact that some regions of foetal and maternal DNA have different levels of “methylation”, which is a chemical modification where a methyl group is attached to the DNA. The researchers say that other non-invasive methods have been developed to detect these “differentially methylated regions” (DMRs) between maternal and foetal DNA, but that they have some limitations.

What did the research involve?

The test is based on the premise that foetuses with Down’s have an extra chromosome 21 (three instead of two). As such, the researchers expected that foetuses with Down’s would contribute more methylated DNA from this chromosome into the maternal bloodstream. This would result in a higher methylated to unmethylated DNA ratio than in cases where the foetus did not have this extra chromosome.

The study involved 80 women who had blood samples taken between 11.1 and 14.4 weeks of pregnancy. In all cases, whether the foetus had Down’s was confirmed using invasive methods before these blood samples were tested. The researchers took these earlier test results and the matching blood samples from 40 of these women (20 diagnosed with Down’s, and 20 without Down’s) and used them to calibrate their test. The other half of the blood samples remained blinded, and the researchers did not know which ones came from women with foetuses that had Down’s.

The researchers concentrated on looking at 12 areas of DNA that are known to be more highly methylated in foetal DNA than maternal DNA. They used a new technique called “methylated DNA immunoprecipitation” to bind to and separate methylated DNA from non-methylated DNA. They then used standard techniques to compare the ratio of methylated to unmethylated DNA in the sample.

For the 40 women whose samples and test results were used to calibrate the test, 8 of the 12 areas of DNA that were tested had different ratios of foetal DNA to maternal DNA when the foetuses had Down’s compared with when they did not. The researchers used these results to identify the appropriate “threshold” ratio that could accurately identify all 20 foetuses with Down’s
and all 20 without Down’s. This ratio was then applied to testing these 8 DNA regions in the 40 samples in the blinded group.

What were the basic results?

In the known sample, the researchers’ tests could correctly identify the 20 normal pregnancies and the 20 pregnancies with Down’s syndrome. In their “blind” sample of pregnant women, the scientists also correctly identified 26 normal pregnancies and 14 pregnancies with Down’s syndrome. This means that in this study the test had 100% sensitivity (the probability that a test correctly identifies the condition) and 100% specificity (the probability of a test correctly ruling out a condition).

How did the researchers interpret the results?

The researchers say their method has been shown to be 100% accurate in identifying Down’s pregnancies, using a maternal blood sample. They say the method has a higher diagnostic sensitivity and specificity than other methods based on genetic information from blood tests and it is also more accurate than current screening methods that use nuchal translucency (a special scan of the foetus) and biochemical markers.

They say that the method can be carried out in basic diagnostic laboratories and is technically easy to perform and low cost compared with other genetic technologies. As such, they suggest that it could be used routinely in all pregnancies, avoiding the risk of miscarriage associated with current procedures.


This small study shows promise in the development of a non-invasive method for detecting Down’s syndrome pregnancies. Currently, the condition is diagnosed prenatally using invasive methods that carry a risk of miscarriage, such as amniocentesis and chorionic villus sampling. The discovery of foetal DNA in the maternal bloodstream has led scientists to investigate whether genetic diseases can be diagnosed using a maternal blood test, thus avoiding the need for an invasive test and the associated risks. This is the latest in a number of studies investigating such tests.

This genetic test shows promise in this early trial, identifying foetuses with Down’s syndrome with 100% accuracy. However, only 14 foetuses with Down’s were included in the blinded part of the trial. Further research involving larger numbers of samples will be needed to assess the accuracy and reliability of this test, and to determine whether it performs well enough to replace current methods.

Although these methods need further testing, it seems feasible that at some point in the future, pregnant women could be offered a blood test that can diagnose certain genetic disorders without the need for invasive testing.

Analysis by Bazian
Edited by NHS Choices