NIPT – Non Invasive Prenatal Testing

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.

Harmony Test is a well known NIPT brand by Ariosa/Roche. Harmony Prenatal Test is a trade name of the cfDNA test. We have experience of using Harmony for many years. Currently there are many other brands of NIPT, which provide similarly reliable results. After careful consideration we have chosen our second NIPT provider which is Invitae NIPS.

Invitae NIPS (non invasive prenatal screening) is an advanced NIPT, which has lower sample failure rate comparing with Harmony Test and its price is much more affordable for the future parents. The limitation of Invitae is its long results reporting time (up to 7 working days) which is a result of sample shipping to California 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.

• Advanced genetic technology
• Less no call results (<2%)
• Better fetal fraction cutoff (1%)
• Works on pregnancies with vanishing twins
• Option of microdeletions screening (an additional $500 payable to Invitae)
• Affordable ($99 for the blood test)

• The most popular NIPT brand in London
• Clinically proven reliability for Down’s syndrome screening 
• Fast test results in majority of the cases just 3-5 working days
• Performed in laboratory located in London
• Option of having fetal sex reveal without running generally not recommended sex chromosome aneuploidy panel

• Long turnaround time: up to 10 working days. It is due to transfer time to California, US based Invitae Laboratory.
• Sex chromosome aneuploidy panel is NOT recommended due to limited clinical validation data, a much higher false positive rate and inconclusive results. The positive or inconclusive results of the test usually NOT covered by NHS and you may require private genetic counselling and possible private invasive test (CVS or amniocentesis) for your own expense.

• Higher cost
• High sample failure rate: 3% suggested by Lab, however real failure rate is more than 5% by our clinical audit of the Lab performance
• Does not work in pregnancies with vanishing twin phenomena

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 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 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 offers NIPT for:

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

At London Pregnancy Clinic we DO NOT routinely offer NIPT for the following conditions, however you can discuss those options with our doctors:

• sex chromosome abnormalities
• 22q11 deletion
• other microdeletions
• triploidy

Some biotechnological companies/manufacturers of NIPT including Invitae NIPS test, which London Pregnancy Clinic offers, have launched commercially available products aiming to screen for sex chromosome abnormalities and microdeletions (including 22q11 del).  

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’ test results as a referral for further invasive testing or genetic counselling.

In London Pregnancy Clinic we strongly recommend to perform Invitae NIPS test without options of sex chromosome abnormalities (sex chromosome aneuploidy panel) and microdeletions.

We recommend to take the NIPT along with our comprehensive early anomaly scan (10 Weeks 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 to perform Viability Scan with us at around 7-8 weeks of your gestation. Viability scan will date your pregnancy and we can arrange earliest possible appointment for your NIPT.

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

In theory, NIPT is available from 10-40 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. 

Following your 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 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 (in this case it is possible to perform Invitae NIPS)
• 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

Turnaround time of Harmony Test in London is about 3-5 working days in 95% of the cases. For Invitae, the tests are sent over to the US and can take up to 5-7 working days.

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

See below information about Harmony test no-call results and need to redraw 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

The main advantages of brand new Invitae NIPS comparing with other NIPT providers are:

• $99 (around £80) test cost which is paid directly to the Invitae Laboratories. 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 (<2%) than other NIPT providers
• Low fetal fraction cull-off (only 1%)
• Pregnancies with vanishing twin phenomena* can be tested by Invitae NIPT
• Additional options for Microdeletions Screening like Di George Syndrome (1p36.3-p36.2, 4p16.3-p16.2, 5p15.3-p15.1, 15q11.2-q13.1 and 22q11.21) for test price $500 and Sex Chromosome Aneuploidies (Turner syndrome and others) for the price of the regular test. Please note that Microdeletions and sex chromosome options are NOT recommended by professional medical bodies and their screening is NOT included in NHS fetal anomaly screening program. Those tests have relatively high chance for false-positive, inconclusive, and false-negative results, which can increase the chance of you having an unnecessary invasive testing with risk of miscarriage, financial loss for NHS-uncovered genetic service and anxiety or false reassurance. 

 The main disadvantages of Invitae NIPS are:

• Longer turnaround time of 5-7 working days because of blood sample transfer to North America-based Invitae Laboratory
• No gender reveal option without having full screening test for sex chromosome abnormalities.

In case the NIPT result is high chance for Down’s / Edward’s / Patau’s syndromes (trisomy21 / trisomy18 / trisomy 13) 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 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 £300) for all our patients with high chance NIPT for trisomy21 / trisomy18 / trisomy 13.

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.

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

In about 3% of cases (more common with Harmony test) 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.

The Harmony scan (and Invitae NIPS) can only be done from a gestational age of 10 weeks – TDL/Invitae do not accept any blood samples for patients below that Gestational Age. We recommend to wait until a gestational age of 10 weeks + 2 days to perform the Harmony/Invitae Scan to avoid having to come in more than once.

In case you booked for Initae/ Harmony Scan, but the ultrasound scan indicated a GA below 10 weeks, 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 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 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.