Non Invasive Prenatal Test (NIPT)-The Harmony™ Prenatal Test
The Harmony™ Prenatal Test
£500-£550 with Miss Bamfo
What is the Harmony Test? Who can have the Harmony Test? How much does the Harmony Test cost ?
Non-invasive prenatal testing (Harmony® test)
The Harmony test is a cell-free DNA-based prenatal blood screen. It is being used in more than 100 countries around the world.
It is a Non Invasive Prenatal Test (NIPT) and has the most advanced screening for Downs Syndrome (Trisomy 21). The test can be used in singleton, twin, and egg-donor pregnancies and has been validated for use in pregnant women aged 18 to 48.
It can be administered as early as 10 weeks gestation. The test can screen for: Trisomies 21, 18, and 13 , fetal sex.
The Harmony test can also screen for X and Y chromosome conditions.
Using a DNA-based technology, the Harmony prenatal test has been shown to identify more than 99% of pregnancies with Down syndrome. By comparison, traditional blood tests can miss as many as 15% of pregnancies with Down syndrome. For more information about accuracy, please see Harmony™ test for Patients and Non-invasive prenatal testing (Harmony® test)
It is paramount to note that The Harmony prenatal test is a screening test. Results should be confirmed with diagnostic testing such as amniocentesis and chorionic villus sampling (CVS).
Non-invasive prenatal testing (NIPT) analyses cell-free DNA circulating in a pregnant mother’s blood. It is used screen for Down syndrome (trisomy 21) and other common chromosomal conditions (trisomies 18 and 13).
TDL Harmony test menu offers the offer the option to screen for X and Y chromosome conditions or for a deletion in chromosome 22q11.2 but we do not routinely offer screening for these conditions at this clinic. This option is not available for twin pregnancies. If the mother is interested in having this optional testing, she should talk with her healthcare provider to determine if it is right for her.
About the test
DNA from the fetus circulates in the mother’s blood. Cell-free DNA (cfDNA) results from the natural breakdown of fetal cells (presumed to be mostly placental) and clears from the maternal system within hours of giving birth.
During a pregnancy, cfDNA can be tested to give the most accurate screening approach in estimating the risk of a fetus having a common chromosome condition sometimes called a trisomy. This occurs when there are three copies of a particular chromosome instead of the expected two.
The cells in our bodies contain genetic material (DNA) that determine how we are made up. The DNA is stored in structures called chromosomes. We have 46 chromosomes (that’s 23 pairs).
The test looks to detect the following conditions:
Trisomy 21 is the most common trisomy at the time of birth. Also called Down syndrome, it is associated with moderate to severe intellectual disabilities and may also lead to digestive disease, congenital heart defects and other malformations.
Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome) are associated with a high rate of miscarriage. These babies are born with severe brain abnormalities and often have congenital heart defects as well as other birth defects. Most affected individuals die before or soon after birth, and very few survive beyond the first year of life.
The testing is non-invasive: it involves taking a blood sample from the mother. The pregnancy is not put at risk of miscarriage, or from other adverse outcomes that are associated with invasive testing procedures such as amniocentesis.
A ‘high probability’ result is indicative of a high probability for a trisomy. In singleton pregnancies, the test identifies more than 99% of fetuses with trisomy 21, 97% of fetuses with trisomy 18, 94% of fetuses with trisomy 13, and 96% of fetuses with Turner syndrome. X and Y analysis provides >99% accuracy for fetal sex. Accuracy for detecting other sex chromosome anomalies varies by condition.
Sometimes the information about the accuracy of a test is mentioned in terms of positive predictive value. Please see the blue box below for more information about this and useful links. For trisomy 21, the Harmony test has been shown to have a PPV of 93% in the high-risk population and 80.9% (95% Confidence Interval 66.7 - 96.9 %) in the general population.
After the test, less than 1% of women need to have a CVS or an amniocentesis procedure.
The Harmony test is considered a prenatal screening test, not a diagnostic test. So if the test results show there is a high risk of the fetus having trisomy 21, 18, 13 or a sex chromosome condition, it does not mean that the fetus definitely has one of these conditions – although it is highly likely. For this reason, in the event of a ‘high risk’ (or positive) result, follow-up testing by an invasive procedure is recommended.
In the same way, if the test results show a ‘low probability’ of the fetus having trisomy 21, 18, 13 or a sex chromosome condition, it is unlikely that the fetus has one of these conditions. However, there is a very small risk that not all trisomic fetuses will be detected.
Who can have this test?
Pregnant women over 10 weeks gestation
This test can be requested for any singleton or twin pregnancy
Natural conception or IVF pregnancies
IVF using the patient’s own egg or a donor egg
Note that, in twin pregnancies, sex chromosome (X and Y) analysis can determine fetal sex but not sex chromosome conditions.
The Harmony test also does not assess risk for mosaicism, partial trisomies or translocations.
On the basis of the NIPT result and the ultrasound findings, a patient can decide whether or not she wants to have an invasive procedure (for example, CVS or amniocentesis).
If you are pregnant and wish to have screening or it has not been possible to do the standard NHS test or missed your combined or quadruple test then the Harmony test would be available if you wish. It can also provide more information whilst deciding on an option of an invasive test. It is important to note that the The Harmony™ Prenatal Test does not replace diagnostic tests such as amniocentesis and chorionic villus sample as those tests are 100% detection. You would still have to consider these to exclude a chromosomal condition. If you chose the Harmony test in this situation your obstetrician/fetal medicine doctor or midwife should be aware and have discussed this with you. The Harmony test does not exclude structural conditions and has limitations if the fetus has a structural anomaly.
Results will be ready in approximately 3-5 days. Women should still have the NHS 12-week scan for a detailed examination of the fetal anatomy, including measurement of nuchal translucency and other important factors.
On the basis of the NIPT result and the ultrasound findings, a patient can decide whether or not she wants to have an invasive procedure (for example, CVS or amniocentesis).
There needs to be enough fetal DNA in the maternal blood to be able to provide a result. If there is insufficient fetal DNA in the sample (which occurs in 3% of cases), another blood sample from the mother may be required. This will be processed in the laboratory at no extra charge.
In other words, in around 4 in 100 women the Harmony blood sample did not contain the minimum amount of cfDNA needed to perform an accurate analysis. This is known Fetal Fraction, and it should be 4%. When a redraw occurs, free of charge, the chance of receiving a screening result on the second draw is 50%. The chance of no result is increased by higher maternal weight as there is a relationship between increased maternal weight an lower cfDNA fetal fraction.
Inconclusive fetal gender: Rarely, this may occur. We are unable to refund the cost of the scan if no test result or if inconclusive fetal gender.
What is the process?
Once the mother has taken an independent personal decision that she wants to have the NIPT performed, she will be asked to sign a consent form (produced by TLD Laboratory) and her blood sample can be taken from a vein in her arm.
Who carries out the analysis of the test?
Her sample and completed request form need to be sent to TDL Genetics, where the Harmony test is performed on the DNA extracted from her blood sample. We send the blood test in addition with your consent form to TDL Genetics who will process the sample. We will arrange a courier to collect the sample if possible or post the sample. The company is a third party company.
Will the mother need to have any other tests?
The Harmony test does not provide information on mosaicism, partial trisomies or translocations, or other rare chromosomal abnormalities. If the ultrasound scan shows a high nuchal translucency or other major physical defects such as brain abnormalities, heart abnormalities, the risk for some rare chromosomal defects may be high. In such cases, the mother may choose to have a CVS or an amniocentesis.
The non-invasive prenatal test does not provide information on other physical defects such as spina bifida, or information on fetal growth. It is therefore advisable that the mother has all the usual ultrasound scans during her pregnancy.
Before booking an appointment, please ensure that you have discussed the Harmony NIPT Test with your doctor or midwife and understood all the implications of the test. This is important as your Healthcare professional would have to interpret and manage any results in the context of your medical and family history. They are also aware of your medical history so if there are any concerns or you are taking medications that may interfere with blood tests, they would be able to inform you. You must be at least 18 years old. You will be contacted by telephone when the results are available. The results will be emailed to you.
We will refer you to your local hospital if the result shows a high probability result.
ARC are a charity that provide useful information and support and you may find their website useful if you are considering the Harmony Test.
When do the results come back?
Results will be ready in approximately 3-5 days but can take around 7 to 10 working days to come back and very rarely 14 days. We will inform you of the results by telephone as soon as they are available and send you a copy of the results by email to share with your own doctor/midwife to interpret taking account of your medical history and family history. If there is not enough DNA in the sample, this could add an additional 3 working days or need a redraw.
What will the results show?
The result may show a low probability or high probability result. A low probability risk means it is unlikely that the baby has Downs syndrome, Edwards Syndrome or Patau’s syndrome.
Any screening has a risk of a ‘false negative’ or being told the risk is low when it is high. However the risk of this happening with the Harmony Prenatal Test is much lower than with conventional Down screening.
A high probability result would means that a chorionic villus sample or amniocentesis would be the only way to find out if the baby has Downs syndrome, Edwards syndrome or Patau’s syndrome. A probability risk result does not mean that the baby definitely has one of these conditions.
Due to the limitations of the test, inaccurate results are possible. A LOW PROBABILITY result does not guarantee that a fetus is unaffected by a chromosomal or genetic condition. Some non-aneuploid fetuses may have HIGH PROBABILITY results. In cases of HIGH PROBABILITY results and/or other clinical indications of a chromosomal condition, confirmatory testing is necessary for diagnosis.
If the Harmony test result is probability or high chance for Down's syndrome or other chromosomal anomalies you will need to be referred to your local Fetal Medicine Unit for further counselling and possible diagnostic test (CVS or amniocentesis). We will refer you to your local Fetal Medicine Unit.
We advise you give your result to your obstetrician/healthcare provider or midwife - this is important so that the report will be interpreted by them as they will have full knowledge of your clinical history and family history and arrange appropriate fetal medicine referral if required
Do I need to have any other tests?
The Harmony Prenatal Test does not provide information on other rare chromosomal abnormalities. If structural abnormalities are found at a later stage of pregnancy the risk for chromosomal abnormality will need to be reviewed as it may be higher. We always recommend having an ultrasound scans at 11-13 weeks and at 20-22 weeks to examine the fetal anatomy.
We always suggest discussing with your Healthcare provider before and after you have the test to ensure it is the right test for you.
By having the harmony test at The Aster Clinic, it is understood that you have been fully informed prior to attending the clinic.
Please note that if an ultrasound scan is performed but we do not proceed to the NIPT or there is no result for the NIPT, a fee of £130 for the viability scan will remain for the appointment.
We always recommend having your usual pregnancy scans with NIPT because fetal structural abnormalities and very rare genetic syndromes will not be picked up by the test.
INCONCLUSIVE NIPT RESULTS
Inconclusive results can occur if there is not enough fetal DNA/low fetal fraction
First inform you healthcare provider and we would recommend you discuss your screening options with them
Repeat sample if you wish after discussing it with your doctor
If the second sample is inconclusive, we advise you inform your doctor and we will refer you to your midwife/doctor to discuss your screening options and for further management.
INCONCLUSIVE GENDER RESULTS
First inform you healthcare provider so that this is interpreted in the context of your medical history and pregnancy
We can book a gender scan at 16 weeks if you wish
Prediction and Limitations of the Harmony NIPT Test
What is the positive predictive value?
Sometimes the information about the accuracy of a test is mentioned in terms of positive predictive value.
Positive predictive value (PPV) is a probability that indicates how likely individuals that screen positive are to be affected by the condition assessed. It depends on both test performance and the prevalence of the condition in a given population.
For trisomy 21, the Harmony test has been shown to have a PPV of 93% in the high-risk population and 80.9% (95% Confidence Interval 66.7 - 96.9 %) in the general population.
For trisomy 18, the Harmony test has been shown to have a PPV of 90% (Confidence Interval 55.5 to 99.7%) in the general population.
For Trisomy 13, the Harmony test has been shown to have a PPV of 50% (95% Confidence Interval 6.3 - 93.2 %) in the general population.
PPV is a population-based statistic and can be interpreted in relation to clinical information.
Online calculators, such as the “NIPT/Cell Free DNA Screening Predictive Value Calculation" attempt to account for this by calculating a theoretical PPV, allowing the user to input an estimated patient-specific prior risk as well as expected test sensitivity and specificity.
The Harmony NIPT has a high negative predictive value (NPV) for Trisomy 21.
Negative predictive value (NPV) indicates how likely individuals that screen ‘negative’ are to be unaffected by the condition assessed and thus provides some reassurance regarding the question.
Does the harmony test rule out a chromosomal abnormality or genetic condition? No it does not.
No. The Harmony NIPT test does not rule out a chromosomal abnormality.
Harmony NIPT is not a diagnostic test and if you wish for certainty then you would need to speak to your obstetrician regarding an invasive diagnostic test such as an amniocentesis.
The harmony test also offers the option of screening for sex chromosome abnormalities or aneuploidies (SCA) and 22q11.2 deletion as an additional option in the Harmony prenatal test menu. NIPT screening for these are not offered by standard NHS screening tests and evidence for clinical use and management pathways is not Robust or clear.
There is no clear knowledge on how good these are or what the results could mean or how to manage the results. This could create uncertainty or lead to additional invasive testing. There may be reduced benefit overall and we are not offering this routinely.
We mention them here because they are on they are on the TDL request form as an option and it is possible for them to be screened for in the private clinics, so you know what is available. However, we do not offer them at this clinic.
You are advised to discuss screening for sex chromosome abnormalities or aneuploidies (SCA) and 22q11.2 deletion with your obstetrician or healthcare professional or genetic counsellor.
For more information, please see TDL and
Who cannot have the Harmony NIPT Test?
Patients who have received bone marrow or organ transplants or those who have metastatic cancer are not eligible for the Harmony Prenatal Test. Patients with a twin pregnancy are not eligible for sex chromosome aneuploidy.
The Harmony Prenatal Test is not validated for use for patients with:
History of or active malignancy
Pregnancy with fetal demise
Pregnancy with more than two fetuses
History of bone marrow or organ transplants
Mosaicism, partial chromosome aneuploidy, triploidy, translocations, maternal aneuploidy
Women under the age of 18.
Women over the age of 48 can not have the Harmony test
The Harmony test does not detect neural tube defects. Certain rare biological conditions may also affect the accuracy of the test.
For twin pregnancies, HIGH PROBABILITY test results apply to at least one fetus; male test results apply to one or both fetuses; female test results apply to both fetuses.
Due to the limitations of the test, inaccurate results are possible.
Can I have the Harmony NIPT Tests available on the NHS?
Currently most NHS hospitals are not offering this. If you are considering antenatal screening, do discuss the NIPT with your healthcare provider.
Do I still need to have the Nuchal scan at 12 weeks if I have had a Harmony NIPT Test? Yes you are advised to have all your NHS scans.
Yes we advise you attend all your NHS screening tests offered during pregnancy even if you have had a Harmony NIPT Test and the Harmony test result reports low probability
At 10 weeks the fetus is still developing and it is important to assess the fetus again at the 12 weeks and at 20 week anomaly scan. The combined test in addition to screening for Down's synfrome will provide information on the early fetal anatomy and measures hormones that give an indication if the fetus will be at risk of growth problems (fetal growth restriction). It may indicate heart conditions or other subtle structural concerns.
Non Invasive Prenatal Testing (NIPT) Dunstable Luton - Bedfordshire Hertfordshire Buckinghamshire
In addition to screening for Down's syndrome and some chromosome abnormalities, the 12 week nuchal scan is recommended because it assesses the early fetal anatomy and measures hormones that give an indication if the fetus will be at risk of growth problems (fetal growth restriction), heart conditions or other subtle structural concerns. We strongly advise you should have all the recommended scans and screening tests offered in the NHS even if you have had a Harmony test NIPT.