Cell Free Fetal DNA Testing

cffDNA Testing

If you have anti-D, anti-C, anti-c, anti-E, anti-e, or anti-K you have another optional blood test. This test can save you time, money, and unnecessary stress. It is called the cell free fetal DNA test or cffDNA for short. This is a blood test where they take mom's blood and find tiny bits of baby's DNA in it. The DNA is isolated and they are able to identify baby's blood type and antigen status (as well as boy/girl). This test is wonderful for women whose anti-Kell may have come from a transfusion, and for those with heterozygous partners. If a woman with anti-Kell has this test done, and it comes back that baby is Kell -, then she does not need extra appointments, costly ultrasounds, or the added stress of an isoimmunized pregnancy. She can have a perfectly normal pregnancy and delivery.

In the US the test is called Sequenome Sensigene (for anti-D moms only). You also have the option of sending blood to the UK or Netherlands to test for Kell, C, c, E, and e. cffDNA testing is now being done in Australia as well as some parts of Canada.

What is it?

cffDNA is a blood test where they draw mom's blood and separate out tiny bits of baby's DNA. This lets them determine baby's antigen status. 


Who should be tested?

Moms who are unable to test dad's phenotype would benefit from the cffDNA test. If dad is heterozygous (Ee or Kk), the cffDNA test would help as well. 


What antibodies is it for? 
In theory cffDNA could be used for all antibodies, however it is only commonly offered for anti-D, anti-C, anti-c, anti-E, anti-e, and anti-Kell.

When is it done?

Around 12-16 weeks of pregnancy. If done earlier, it may need to be repeated later when there's more of baby's cells in mom's system.

Canada: Kell >28 weeks. 16 weeks for D, C, c, E, e.
UK: Kell >20 weeks. 16 weeks for D, C, c, E, e.
Netherlands: Kell 14 weeks. D, C, c, E, e >9 weeks, but prefer 12 weeks or older. 


Why is it done?

To determine baby's antigen status and to find out if baby is at risk of being attacked by mom's antibodies. If baby is negative for the antigen that matches mom's antibody, then baby will be safe. 


How often is it done?

Usually just once unless the test was done too early, then it may need redone again after 14 weeks. They will also repeat a negative test result at 20 weeks just to be sure.


How is it done?

Print out the instructions and the request form  Bring both forms to your doctors office and laboratory. 


Instructions:https://www.sanquin.org/binaries/content/assets/en/products-services/diagnostic-services/diagnostic/instructions-for-non-invasive-fetal-dna-testing.pdf 
Request Form: https://www.sanquin.org/binaries/content/assets/en/products-services/diagnostic-services/diagnostic/request-form-2a-non-invasive-fetal-genotyping


FAQ: https://www.sanquin.org/binaries/content/assets/en/products-services/diagnostic-services/diagnostic/faq-non-invasive-fetal-blood-group-genotyping.pdf


If the above links stop working, try the landing page at https://www.sanquin.org/products-and-services/diagnostics/non-invasive-fetal-blood-group-genotyping

What do the results mean?

If baby is positive, then he is at risk of being attacked by the antibodies and developing Hemolytic Disease of the Fetus and Newborn. If he is negative, then baby is safe.


When should I get additional monitoring?

You will need additional monitoring if your baby comes back as being positive for the antigens that match your antibodies. 

What risks are there?

The risks with the cffDNA test are the same with any blood draw.

What are the benefits?

If baby is negative for the antigen that matches mom's antibody, then baby will be safe. Benefits include decreased cost (no MCA ultrasounds needed, no weekly appointments, travel, etc), more free time (less going to appointments), and less stress for the family. There is also no risk of loss, hemorrhage, or an increase in titers unlike with an amniocentesis or chorionic villus sampling. 


Additional Info

If you are not in a country that does cffDNA testing for the antigens matching your antibody, blood is shipped to the Netherlands or the UK. See the Sanquin link below for information on sending blood to the Netherlands. Current cost (2019) is 800 Euros for the testing. Insurance may cover it if you and your doctor write letters explaining the disease and potential costs (ie each Level II Ultrasound costs $900 at 1 per week for 20 weeks that's $18,000 the insurance company can save if baby is tested and found to be negative).

If you have ANY antibody that is not anti-D, and your blood type is A-, AB-, B-, or O-, GET YOUR RHOGAM! If you have anti-D and anti-C together, get it checked to be sure that it is not really anti-G. If you have anti-D and anti-C, you may still need Rhogam if it is really anti-G.

How to submit blood for the cffDNA test

Links

Article about the usefulness of cffDNA:  https://losinglucyandfindinghope.files.wordpress.com/2016/12/scheffer_et_al-2011-bjog__an_international_journal_of_obstetrics__gynaecology.pdf

USA Sensigene RhD test website:  https://www.sequenom.com/tests/reproductive-health/sensigene-rhd

Australian Red Cross Non-Invasive Prenatal Analysis (NIPA) for RhD website:  https://transfusion.com.au/node/809

Neatherlands Sanquin website:  https://www.sanquin.org/products-and-services/diagnostics/non-invasive-fetal-blood-group-genotyping

UK Testing for those in the NHS system: https://ibgrl.blood.co.uk/services/user-guides/ Click on "Fetal RhD Sampling" for anti-D, and click on "Molecular Diagnostics" and "Fetal Genotype Sample Referral Form". 
Canadian Blood Service:  https://blood.ca/en/laboratory-services/fetal-genotyping-maternal-plasma-0