Harmony Test Summary
- Currently the best screening test for Down's syndrome
- Can be done from 10 weeks of pregnancy
- Performed together with ultrasound scan at the same appointment
- Not able to exclude physical (structural) anomalies
- In 3% of cases there is no-call result
- If the NIPT is positive further referral/testing will be needed
- We recommend to use Harmony as an integral part of Early Baby Test at 12 weeks
- City Ultrasound Harmony Test cost is very competitive
What is NIPT? What is Harmomy test?
Non Invasive Prenatal Testing (NIPT) is a screening method for determining the chance that the baby will be born with Down’s syndrome or other particular chromosomal anomaly. NIPT is based on assessment of small DNA fragments from baby's placenta (so-called cell-free DNA or cfDNA) that are disseminated in the blood of every pregnant mother. Placental cfDNA is usually identical to the DNA of the baby and testing it provides an opportunity for early detection of particular chromosomal anomalies without harming the baby.
Harmony Test is our single and carefully selected NIPT laboratory provider. Harmony Prenatal Test is a trade name of the cfDNA test.
Although cfDNA is a relatively new genetic test, it has been proved to be superior than any other screening tests for Down’s Syndrome, including the Combined Screening Test (CST) used by the NHS. That said, NIPT can detect just a relatively small proportion (about 15%) of all fetal anomalies, because vast majority of fetal anomalies are physical (structural) and not chromosomal.
NIPT is a screening test meaning that NIPT cannot give a definitive answer about whether or not a baby has Down’s syndrome or other tested chromosomal condition. If the results are positive (high chance) follow-up invasive testing is needed to get a definite diagnosis. Any invasive test carry a small risk of miscarriage.
What are the advantages of NIPT?
The main advantages of NIPT are related to Down's syndrome (T21) screening.
- early testing from 10 weeks
- works at any stage of pregnancy after 10 weeks
- high negative predictive value for T21
- high detection rate for T21
- low false-positive rate for T21
What are the limitations of NIPT?
As any screening test NIPT has some disadvantages.
Here there are the most significant NIPT limitations:
- relative high cost of the cfDNA test
- very sensitive screening test, however not diagnostic
- inability to detect ANY physical (structural) anomaly
- very limited effectiveness for the babies that have increased nuchal translucency (NT) thickness or physical (structural) anomaly
- long period to receive blood test results: generally up to one week
- failure to return a result in up to 3% of women (‘no-call’ results)
NIPT is currently the BEST screening test for Down's Syndrome and its main limitation is that it reliably screen ONLY for Down's Syndrome
Performance of the NIPT for Down's Syndrome in numbers:
- the most clinically important feature of NIPT is its high negative predictive value (NPV). Negative predictive value indicates how likely screen ‘negative’ babies in reality have no Downs syndrome. High negative predictive value provides reassurance regarding the question of how likely a baby with low chance result has no Downs syndrome. For Harmony test calculated NPV is at least 99.3% and generally greater than 99.9%
- test for Down’s syndrome is 96% accurate in most pregnant women. This means the test will identify 96 out of 100 women who have a baby with Down’s syndrome. The test is even more accurate in women with a higher than normal chance of having a baby with Down’s syndrome
- Although the test is very accurate, sometimes it shows a positive result when the baby does not in fact have Down’s syndrome. Around 20% (1 in 5) of positive results are false in this way
- high detection rate for T21 >99%
- low false-positive rate for T21 ~0.02%
NIPT for sex chromosome abnormalities and microdeletions: inconclusive
Some biotechnological companies-manufacturers of NIPT have launched commercially available products aiming to screen for sex chromosome abnormalities and microdeletions (including 22q11 del).
Although the tests are technologically advanced, the effectiveness of those extended panel options has not been confirmed by appropriate scientific research and at this moment their clinical use is controversial.
As technology improves and the cost of NIPT decreases, we expect that cfDNA test will become clinically useful not only for Down's, Edwards and Patau syndromes and also for many more chromosomal and genetic conditions. However at the moment the majority of experts agree that the time has not come yet.
For which chromosomal conditions does we offer NIPT?
City Ultrasound offers NIPT for:
- Down's syndrome (T21)
- Edwards syndrome (T18)
- Patau syndrome (T13)
- fetal sexing
City Ultrasound does not offer NIPT for:
- sex chromosome abnormalities
- 22q11 deletion
- other microdeletions
Is it beneficial to perform NIPT and Viability Scan at 10 weeks? Not sure.
We are aware that many of NIPT providers advise to perform NIPT at 10 weeks together with viability scan. The obvious advantage of this approach is the fact that NIPT performed as early as possible.
In our opinion this approach is imprecise and have serious limitations because at 10 weeks:
- The baby is an embryo, it has not finished the development and it is impossible examine its anatomy to exclude physical (structural) anomalies, which can be very serious or even lethal. Statistically, the chance of the baby to have structural anomalies is much higher than chance for Down's syndrome.
- It is impossible to assess nuchal translucency (NT) thickness, which is an independent nonspecific marker for fetal wellbeing. The baby with increased NT has increased chance for chromosomal anomalies even if NIPT results are negative and the invasive test is offered.
In reality there are unfortunate situations when the parents have spent significant amount of money for private NIPT, which was negative and 'reassuring'. However the baby has significant health problem, which was diagnosed just few days or weeks later.
To avoid those situations and to provide our patients the best possible screening option we have developed Early Baby Test at 12 weeks: the combination of Early Fetal Scan and NIPT.
Harmony Test and Early Baby Test Comparison Chart
Harmony Prenatal Test is City Ultrasound selected NIPT
There are many different brands of cfDNA tests on the private NIPT London market. We believe that to make the correct NIPT choice can be very confusing for the parents and difficult even for medical professionals.
We have evaluated and compared different NIPT brands available in London and have chosen Harmony Prenatal Test as our exclusive provider. We have extensive clinical experience of using Harmony.
The facts about Harmony:
- the test was developed in US by Ariosa Diagnostics
- It is one of the most popular NIPT tests around the world
- In London the test is now being undertaken by TDL (The Doctors Laboratory)
- Relocation to London resulted in reduction of Harmony Test cost and decrease in turnaround time
How long does Harmony Test results take?
Turnaround time of Harmony Test in London is about 3-5 working days.
From our clinic the sample is securely taken by special medical courier service.
The blood sample is analysed in TDL (The Doctors Laboratory). TDL Genetic is located in high-tech establishment on Euston Road just few minutes ride from our centre.
See below information about Harmony test no-call results and need to redraw the blood sample (no additional cost).
Early Baby Test: Early Fetal Scan and NIPT at 12 weeks of pregnancy
We introduce Early Baby Test a new generation screening test which organically includes Early Baby Scan (Early Fetal Scan) and Harmony (NIPT).
This 1 trimester reassuring package provide a unique 12 weeks screening solution by combination of two innovative tests where ultrasound & NIPT are working together to exclude significant proportion of physical (structural) and chromosomal anomalies (T21, T18, T13) for your baby.
How Early Fetal Test works?
- You book appointment for the package at 12 weeks via our online booking system.
- You do not need to have full urinary bladder for the scan.
- Firstly we perform Early Fetal Scan and will confirm gestational age and well-being of the baby, we will perform top-to-toe examination of fetal organs with special attention to heart and brain/spine. we will measure nuchal translucency (NT) thickness.
- If everything is fine we will inform you about normal findings and reassure you. We will write you ultrasound report and send you special access code for your baby's images on safe cloud storage.
- Secondly, we will give you full explanation regarding Harnomy Test (NIPT). We will take your blood sample for Harmony Test. You do not need to have any specific preparation for the test. The sample will be taken by courier same day or next morning to TDL.
- TDL (The Doctors Laboratory) is a major high-tech laboratory service provider in UK. It is situated on Euston road, London. They will start to proceed your sample as soon as possible. It takes few days to perform cfDNA analysis for NIPT.
- TDL will send us result and we will contact you immediately. NIPT is the most time consuming test that TDL performs and usually it takes up to one week to get the results.
How do we perform NIPT and give results?
We will provide you information about the test and will answer your questions. You will need to sign the consent form.
After we will firstly perform a scan in order to check normal development of the pregnancy, number of babies and baby's viability. If you choose our recommended Early Baby Test, we will perform top-to-toe examination of the baby, to exclude severe physical anomalies, which Harmony Test is unable to detect.
If the scan results are normal we will take your blood sample. There is no need to freeze the blood sample and the tube will be taken by special courier to TDL.
After few days, (usually less than one week) TDL will securely send us result and we will contact you by phone as soon as possible. We will also send you a PDF copy of the via Tricefy.
Who is NOT eligible for Harmony Test?
The Harmony Prenatal Test is not validated and can not be use for use in pregnancies with:
- a history of or active malignancy
- a pregnancy with fetal demise
- a pregnancy with triplets, quadruplets or higher order
- a history of bone marrow or organ transplants
- mosaicism for the parents
- maternal aneuploidy (chromosomal abnormality)
- in women under the age of 18
Please note that IVF pregnancies are eligible for Harmony Test
What to do if NIPT results shows high chance for chromosomal anomaly?
If unfortunately the NIPT result is high chance for Down's syndrome or other chromosomal anomalies you need to be referred to your regional NHS Fetal Medicine Unit for further counselling and possible diagnostic test (CVS or amniocentesis).
Alternatively we can refer you to private Fetal Medicine Consultant (consultation cost is not included in our service).
What are the reasons for Harmony Test false positive results?
Although the Harmony Test is very accurate, around 20% (1 in 5) of positive high chance for Downs syndrome results are false and the baby does not in fact have Down’s syndrome.
Biological factors with the potential to cause discordance between cfDNA results and baby's genetic status include uncommon conditions like confined placental mosaicism, fetal mosaicism, maternal chromosome changes, and the presence of an unrecognised, nonviable (or viable) twin.
What does it mean Harmony test no-call results?
Most pregnant women receive complete results from cfDNA testing, indicating either a high or low probability for aneuploidy.
In about 3% of cases we will need to contact you without giving you a test result and ask to come for additional sample of blood or to give us more information about your pregnancy or medical history. There will be no extra cost for additional blood test.
It is because in small proportion of blood specimens submitted after 10 weeks gestation there is insufficient amount of baby's cfDNA. This situation called low fetal fraction. The chance to have low fetal fraction is getting higher with increased maternal body weight. There are other rare factors making NITP results inconclusive.
In the case of Harmony Test no-call results we will discuss with you options of alternative screening and/or referral for diagnostic testing if you either decline a second attempt at NIPT or do not receive a result after two attempts.
Our Harmony test no-call results refund policy
In the case of inconclusive results for Downs syndrome or trisomies 18 or 13 we are committed to refund your for the Harmony Test cost.
Because the Harmony Test is being undertaken by third party - TDL (The Doctors Laboratory) we will contact them to arrange the refund. The refund will be for Harmony Test only (we can not compensate cost of ultrasound) and will be processed in a few business days.
There is no reimbursement for inconclusive fetal sex results. In those rare cases we will offer you anatomy and gender scan for reduced cost and will discuss the findings and need for further referrals.
Harmony Test Cost and Refunds
Unfortunately clinically validated NIPT tests are time consuming and very expensive. City Ultrasound Harmony Test cost is very competitive. We have made maximum effort to make the Harmony Test + Scan affordable.
The Harmony Test (NIPT) can only be done from a gestational age of 10 weeks –TDL would not accept any blood samples for patients below that GA. In case you booked for the Harmony Test, but the ultrasound scan indicated a GA below 10 weeks, we will be happy to reschedule for you to come in another day for us to draw the blood samples. In case of No-Call results from the test (about 3% of the cases), we will be happy to schedule in another time to draw another blood sample free of charge. In case of a second No-Call result, we will refund the Harmony Test portion of the appointment charge as per below. If, upon discussion with our clinician, you decide that the Harmony Test is not the right decision for you, we will refund the Harmony Test proportion of the appointment and will only charge for the scan.