Early work on baby screening blood test

Thursday December 9 2010

Scientists have devised “a blood test that could predict an unborn baby's risk of numerous disorders”, the Daily Mail has reported. The newspaper said a tiny sample of the mother's blood can be used to piece together the child's entire genetic code and search for conditions such as Down's syndrome and autism.

At present, genetic tests for unborn babies rely on invasive methods, requiring a sample to be taken of the placenta or the amniotic fluid surrounding the foetus in the womb. This research aimed to develop an alternative technique that can analyse fragments of foetal DNA in the mother’s blood and potentially avoid the need for invasive testing. However, this is still a research technique and is not yet ready for practical use. It is important to note that the researchers still needed to use some information from invasive placenta sampling to carry out their analyses.

Overall, this interesting study brings us one step closer to the possibility of non-invasive foetal genetic testing. However, much more development and testing of this prototype method will be needed before it could replace existing methods.

Where did the story come from?

The study was carried out by researchers from the Chinese University of Hong Kong and Sequenom Inc from the USA. The study was funded by the Hong Kong Research Grants Council, Sequenom, the Chinese University of Hong Kong and the Government of the Hong Kong Special Administrative Region, China.

The study was published in the peer-reviewed journal Science Translational Medicine.

The study was reported in the Daily Mail and The Daily Telegraph. Both papers importantly highlighted some of the risks associated with invasive testing and the ethical issues surrounding prenatal testing. Although other studies have tested a similar technique to detect conditions such as Down’s syndrome, in which an individual carries an extra chromosome, the current study only looked for changes within the genetic sequences of chromosomes. It is not clear whether this particular technique is suitable for detecting this type of chromosomal genetic change. The Mail also mentioned autism, but the causes of autism are not clear, so genetic testing for this condition is unlikely to be useful at the moment. The Mail also noted the high cost of such a test, which they estimate would cost £125,000 for each baby.

What kind of research was this?

This laboratory study aimed to develop ways to look at the genetic make-up of a foetus using a blood sample from its mother.

Looking at the genetic make-up of a foetus currently requires the use of invasive techniques, taking a sample of the amniotic fluid surrounding a foetus or a tissue sample from the placenta. In 1997, it was discovered that some of the foetus’ DNA circulates in the mother’s blood stream. If researchers could develop a way to distinguish this from the mother’s own DNA, this could allow non-invasive genetic testing of the foetus. The current study aimed to do this.

What did the research involve?

The researchers took blood samples from a pregnant woman and her partner who were attending a genetic clinic for prenatal diagnosis of beta thalassemia, a blood condition caused by carrying two mutated forms of the beta-globin gene. The mother and father each carried one mutated copy of the beta-globin gene. Their baby would have a one in four chance of inheriting both these mutated copies of the gene and, therefore, being affected by beta thalassemia (carrying only a single copy of the mutated gene does not usually lead to any symptoms). As well as providing blood samples for the study, the family also received conventional genetic testing using a sample of placental tissue, which researchers also used in their analysis.

The key to the research was to be able to distinguish between the mother’s DNA in her bloodstream and the fragments of DNA in her blood that came from the foetus. This was mainly done by checking the DNA samples from the blood for genetic information that could only have been inherited from the father, therefore indicating that it had come from the foetus.

To do this, the researchers determined the genetic sequence of specific sites in DNA extracted from the mother’s and father’s blood samples, as well as from the foetal DNA found within the placental tissue.

They then used information about the father’s and mother’s DNA sequence to identify those DNA sequences in the mother’s blood sample that must have belonged to the foetus. They could verify their findings using foetal DNA from placental tissue, and use information from this DNA to help their analysis in other ways. They then used computer programs to identify overlaps between the foetal DNA fragments identified in the maternal blood sample, similar to re-constructing a book from overlapping fragments of sentences.

They used their methods to see whether they could determine from DNA from the maternal blood sample whether the foetus had inherited the beta-globin gene mutations from the parents.

What were the basic results?

The purpose of the research was firstly to be able to distinguish between the maternal and foetal DNA from the maternal blood sample and to see if the foetus’ entire DNA sequence was present. The second objective was to determine the test’s ability to detect beta thalassemia in the foetus.

The researchers found that foetal DNA in the mother’s blood stream broke down into predictably sized fragments, and that these fragments differed in size from those from the mother. The researchers also found that these fragments together covered most of the foetus’ DNA.

The researchers also looked specifically at sites in the maternal blood sample DNA where the father had carried two identical copies of a sequence that differed from the mother’s genetic sequence. For about 94% of these sites, they could identify foetal DNA because it carried a sequence inherited from the father.

In terms of diagnosis, the prediction from the maternal blood sample agreed with the results of conventional invasive sampling. The foetus had inherited the father’s beta-globin gene mutation, but not the mother’s mutation. This meant that the foetus would not be affected by the condition.

How did the researchers interpret the results?

The researchers concluded that their results mean it is feasible to test for genetic disorders in a foetus using a non-invasive maternal blood sample.


This study has shown that it should be possible to test foetal DNA using maternal blood samples. However, there are some points to note:

  • This study only looked at samples from one couple to establish whether the method could work. This does not tell us how well it would perform if used more widely. Before the technique could be widely used, it would have to undergo further testing in more couples and for other conditions to ensure that it was accurate and reliable enough for general use.
  • The method relied partly on information obtained from foetal DNA from sampling of the placenta (chorionic villus sampling). If the new method was to replace this type of invasive testing, this information would need to be obtained in a different way. The researchers suggest ways in which this could be done, for example by looking at DNA from family members or by using different methods to analyse the mother’s DNA. These alternative methods would need to be assessed to ensure they could reliably provide the information needed.
  • The method used in this study required a very large amount of DNA sequencing and piecing together of these sequences. Although this is largely automated, it is currently unlikely to be feasible to do this full analysis for standard foetal genetic testing because of the time and resources needed. However, as the technology advances, this may change.
  • In this study, the technique was used to assess whether the foetus had inherited copies of the beta-globin gene that carried mutations (either a change in a single “letter” of the genetic code or a deletion of four letters). While this means that other diseases caused by similar types of mutations in a single gene could be identified using this technique, it is not clear whether it could be used for conditions caused by carrying an extra copy of a chromosome, such as Down’s syndrome.
  • The researchers note that although their new technique would reduce the risks to the foetus associated with invasive testing, there would still be a number of legal, ethical and social issues. This would include how to provide genetic counselling for such a complex test, and what types of genetic characteristics or abnormalities it would be ethical to test for. They suggest that this will require extensive discussion between doctors, scientists, ethicists and the community.

Overall, this interesting study brings us closer to the possibility of non-invasive foetal genetic testing. However, much more development and testing of this method will be needed before it could replace existing ones.

Analysis by Bazian
Edited by NHS Choices