It’s important for us that you understand the terminology we use for screening tests:

Detection rate is defined as the fraction of all patients who have the disease and are called positive by the screening test.

Positive Predictive Value or PPV is the proportion of the ‘true positives’ as proportion of all positive results. As a practical example, the Panorama AI test has a 95% PPV for Down’s Syndrome, meaning that 95% of the fetuses identified as ‘High Probability’ will statistically have the condition. However, the limitation of the test is that in 5% of the cases, it will result in a ‘false negative’ meaning that the test will return a ‘High Probability’ result for a fetus that doesn’t have Down’s Syndrome.

That’s why, for every High Probability result we would refer the patient for a diagnostic test such as CVS or Amniocentesis to verify the results.

In the past there has been confusion about certain aspects of NIPT – please see this notice. If any of the above still unclear to you, please get in touch with us via email or phone and our friendly stuff will be happy to run you through the characteristics of the test.

We wrote a special blog post about understanding the statistics of the NIPT test,  if you would like to find out more, click here.

Non-invasive prenatal testing (NIPT) or alternatively non-invasive prenatal screening (NIPS) is a screening method for determining the chance that a baby will be born with Down’s syndrome or other chromosomal anomalies. NIPT is based on the assessment of small DNA fragments from a baby’s placenta (named ‘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.

The Harmony Test was a well-known NIPT brand by Ariosa/Roche. The Harmony Prenatal test was a trade name of the cfDNA test. We had the experience of using Harmony for many years. The Harmony Test performed by TDL in London in the last years suffered from a high rate of test failure and inconclusive results. Many our patients were unsatisfied by the test performance. In a dramatic move at the end of August 2023, TDL announced the termination of the test performance in a very short warning period of just two weeks.

Panorama AI NIPT (non-invasive prenatal screening) is an advanced NIPT, based on state-of-the-art algorithms, it has lower sample failure rate comparing with the harmony test and its price is more affordable for the future parents. The limitation of panorama NIPT is its long results reporting time (up to 10 working days) which is a result of sample shipping to US based Lab. 

Although cfDNA is a relatively new genetic test, it has been proven to be superior to any other screening tests for Down’s syndrome, including the combined screening test (CST) used by the NHS. However, NIPT can detect a relatively small proportion (about 15%) of all fetal anomalies, because the 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 a baby has Down’s syndrome or other tested chromosomal conditions. If the results are positive (high chance) follow-up invasive testing is needed to get a definite diagnosis. Any invasive testing carries a small risk of miscarriage.

Harmony Test was discontinued by its provider in London UK (The Doctors Lab – TDL) presumably due to its unsatisfactory performance.

During September 2023, The Doctor’s Laboratory (TDL Genetics) who had the exclusive rights for performing the Harmony Test NIPT in the UK, announced that it had ceased offering the test. 

As an alternative, the laboratory opted to offer VeriSeq™ NIPT Solution v2 which has been used by other laboratories in the UK for a couple of years. At London Pregnancy Clinic, we chose to use PrenatalSAFE, that uses the same apparatus as Illumina’s NIPT test, but has better validation data and more experience with using the technology.  

• Advanced genetic technology
• Whole-Genome Sequencing (WGS)
• Proved performance for Down’s syndrome screening
• Less no-call results (<2%)
• Fast results: 3-5 working days

• Advanced genetic and artificial intelligence (AI) technology
• Available from 9 weeks
• Di George Syndrome (22q del) screening
• Triplody screening
• Less no call results (1.4%)
• Better fetal fraction cutoff (2.8%)
• Option of additional microdeletions screening (for an additional fee)
• Option of additional single-gene mutations across 30 genes screening by Vistara NIPT (for an additional fee)
• Cheaper option at £200 (vs £240)

22q deletion (del) syndrome or Di George syndrome is a genetic condition, which is caused by a small, missing or “deleted” piece of the 22nd chromosome. Unfortunately, that missing piece can affect every system in the human body including the heart (heart defects in 75% babies), palate, immune system, hormones, kidneys and others. It also can affect mental health and is associated with learning and behavioural differences, anxiety, and other mental health issues like schizophrenia (in 25% of adults).

Panorama AI can detect >80% of the fetuses with 22q del with a positive predictive value of 53%. Early detection of 22q del can lead to earlier interventions and better outcomes for affected individuals. For instance, in our clinic, we can perform early fetal echocardiography from 12 weeks to exclude severe heart anomaly associated with 22q del.

For more information, please visit www.22q.org

• Longer turnaround time: up to 10 working days. This is due to the time taken to transfer the samples to the US based lab.
• Application of extended diagnostic panels (sex chromosomes, triploidy, 22q del, microdeletions) increase the chances for false positive and inconclusive results. The positive or inconclusive results of the test in some cases do NOT covered by NHS and you may require private genetic counselling and possible private invasive test (CVS or amniocentesis) for your own expense.

Unfortunately Harmony in London in the last few years had many limitations, which have prompted its provider TDL to terminate its performance.

Currently NIPT is not routinely offered by the NHS.

The nuchal translucency (NT) thickness measurements scan was developed in the 1990s, and at the time was the best screening option for Down’s syndrome offering about 62% accuracy and a 5% false positive rate. The NHS now offers the ‘combined test’ at 11-14 weeks which includes a nuchal translucency scan along with a blood test (for PAPP-A and HCG proteins) with improved the accuracy of 81% and false positive rate of 4.5%.

NIPT was first introduced in 2011 and was shown to have superior accuracy to the combined test with a 99.99% detection rate and sub 0.1% false negatives. Please note, we still recommend following through with your NHS antenatal appointments, they are important for the continuity of your pregnancy care.

We offer NIPT for the following:

• Down’s syndrome (T21)
• Edwards syndrome (T18)
• Patau syndrome (T13)
• fetal sexing

Some biotechnological companies/manufacturers of NIPT, including Panorama AI and UNITY, which London Pregnancy Clinic offers, have launched commercially available products aiming to screen for sex chromosome abnormalities, microdeletions (including 22q del) and/or single-gene disorders.

Although the tests are technologically advanced, the peer-reviewed validation data for those tests is patchy, and the accuracy is inferior to the tests for T21, T18 and T13.

In the UK, the NHS considers the use of those tests controversial and, as such, unlikely to accept a ‘high probability’ or ‘inconclusive’ test results as a referral for further invasive testing or genetic counselling.

If you choose to have those advanced options, we will guide you and arrange private genetic counselling in the case of high-chance NIPT results. Please note that this can incur additional expenses. 

We recommend taking the NIPT along with our comprehensive early anomaly scan (10-week scan) as soon as possible – 10 weeks. Early detection of either chromosomal or structural anomalies allows more time in terms of pregnancy management for those conditions. If your sample fails, you have plenty time for redraw.

If you’re unsure about the age of your pregnancy, we strongly recommend performing a viability scan with us at around 7-8 weeks of your gestation. The viability scan will date your pregnancy and we can arrange the earliest possible appointment for your NIPT.

If you’d prefer not to have the viability scan, please allow a couple of days after the 10-week mark to avoid repeat appointments for drawing the bloods. You can also miss all the advantages of the 10-week scan, because your baby will be too young to have a proper early anomaly scan. 

In theory, NIPT is available from 9-40 weeks, but it is strongly recommended to take the test in the first trimester, as the pregnancy management options in the second trimester can be very limited. 

Yes, you can. Panorama AI works from 9 weeks. Please note that in this case, structural assessment of the baby by ultrasound can be limited and we will be unable to screen for some very serious conditions like holoprosencephaly or spina bifida. If you wish to have NIPT before 10 weeks, please consider a scan from 9 weeks 4 days.

Following your ultrasound scan appointment, you will receive a detail scan report from our doctors, as a hard copy and a PDF version sent to you via our secure cloud system Tricefy.

As soon as we receive your NIPT test results from the laboratory, our clinician reviews the test results and signs them off. One of our friendly clinical staff will then contact you via a phone call to interpret the test results. We will then send you a soft copy of the test results via Tricefy.

The majority of NIPT are  NOT validated and cannot be used in pregnancies with:

• a history of or active malignancy
• 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 a NIPT

Turnaround time of the harmony test in London is about 3-5 working days in 95% of the cases. For panorama, the tests are sent over to the US and can take up to 5-9 working days.

From our clinic the sample is securely collected by a specialist medical courier service.

See the below information about the harmony test no-call results and redrawing the blood sample (no additional cost.)

The main advantages of NIPT are related to Down’s syndrome (T21) screening.

They are:

• early testing from 10 weeks
• high negative predictive value for T21
• high detection rate for T21
• low false-positive rate for T21

As any screening test NIPT has some disadvantages.

Here there are the most significant NIPT limitations:

• relative high cost of the cfDNA test (Harmony Test)
• whilst a very sensitive screening test, it is not diagnostic
• cannot detect ANY physical (structural) anomaly
• very limited effectiveness for the babies that have increased nuchal translucency (NT) thickness or physical (structural) anomaly
• processing time of up to a week (or longer in 5% of the cases) or even 10 days for Invitae NIPS
• failure to return a result in up to 5% of women (‘no-call’ results) which is more common for Harmony Test

Currently, we consider PrenatalSafe as the best option for NIPT in London, because it provides advanced technology, low no-call results, and a short turnaround time (the lab is UK based). PrenatalSafe can be considered the best replacement for the outdated Harmony Test.

Pros:

• advanced technology
• reliable screening for Down’s syndrome
• uses a small amount of maternal blood
• short turnaround time
• low no-call rates
• works for vanishing twin syndrome
• highly reputable in Europe

Cons:

• Limited experience using the test in London

The main advantages of the brand-new panorama AI algorithm comparing with other NIPT providers are:

• £200 test cost. This transparent price solution makes our combination of expert ultrasound scan and NIPT to be the most advanced and cost-effective option for early reassurance of the parents
• Fewer no-call results (1.4%) than other NIPT providers
• Low fetal fraction cull-off (only 2.8%)
• Extended diagnostic panel: option to screen for Di George Syndrome ( 22q del), Turner syndrome, triploidy and other conditions for an additional fee. 

 The main disadvantages of Panorama Test are:

• Longer turnaround time of 7-10 working days because of blood sample transfer to North America-based Natera Laboratory.
• Higher chance for false-positive and inconclusive results.

In case the NIPT result shows a high chance for Down syndrome or other conditions, our doctor will contact you and explain the further steps we advise to take. We will most likely arrange a referral to your NHS fetal medicine unit for further counselling and possible diagnostic test such as CVS or amniocentesis.

Alternatively, we can refer you to a private fetal medicine consultant (consultation cost is not included in our service).

We will also offer early fetal echocardiography for free (regular cost of the examination £320) for all our patients with high chance NIPT for trisomy 21, Di George syndrome, trisomy 18, trisomy 13 and Turner syndrome.

Although our NIPT options are very accurate, some positive high chance for Downs syndrome results are false and the baby does not in fact have trisomy 21.

Biological factors with the potential to cause discordance between cfDNA results and the 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.

Most pregnant women receive complete results from cfDNA testing, indicating either a high or low probability for aneuploidy.

In about 3% of cases (much more common with a harmony test) we will need to contact you without giving you a test result and ask you to come in for an additional sample of blood or to give us more information about your pregnancy or medical history. There will be no extra cost for an additional mother’s blood test.

It is because in small proportion of blood specimens submitted after 10 weeks gestation there is an insufficient amount of the baby’s cfDNA. This situation is 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 a harmony test no-call result, we will discuss 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.

The harmony scan can only be done from a gestational age of 10 weeks, while panorama NIPT can be done from 9 weeks. TDL/Natera do not accept any blood samples for patients below that gestational age. We recommend waiting until a gestational age of 10 weeks + 2 days (9+4 for panorama) to perform the harmony/panorama scan to avoid having to come in more than once.

In case you booked for a panorama/harmony scan, but the ultrasound scan indicated a GA below 9/10 weeks (respectively), we will have to rearrange for you to come in at a later date for an additional cost of £50 to cover for our staffing cost.

In the 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.

In the case of inconclusive results for Downs syndrome or trisomies 18 or 13, we are committed to refunding the harmony test cost.

Because the harmony test is being undertaken by a third party, TDL (The Doctors Laboratory), we will contact them to arrange the refund. The refund will be for the harmony test only (we cannot compensate the 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 an anatomy and gender scan for a reduced cost and will discuss the findings and need for further referrals.

Vanishing twin is a situation with twin pregnancies when the embryo or fetus in one of the sacs fails to develop or dies at the early stages of pregnancy. Interpretation of NIPT in the case of a vanishing twin phenomenon is complicated due to contamination of the sample by DNA of a non-developing twin pregnancy.

Our advanced NIPTs: PrenatalSafe and UNITY can be used in this situation.

Delaying the NIPT by five weeks is a recommended approach to reduce the chances of false-positive results associated with the vanishing twin syndrome.