PrenatalSAFE Test in London 

Non-Invasive Prenatal Testing (NIPT), also known as Non-Invasive Prenatal Screening (NIPS), is an assessment method used to determine the likelihood of a baby being born with conditions like Down’s syndrome or other chromosomal anomalies or single gene disorders. NIPT relies on analyzing tiny DNA fragments from the baby’s placenta, referred to as ‘cell-free DNA’ or ‘cfDNA,’ which circulate in the bloodstream of pregnant mothers. This placental cfDNA is typically identical to the baby’s DNA, offering a means to identify certain chromosomal anomalies at an early stage without posing any risk to the baby.

It’s important to note that NIPT is a screening test, implying that it does not provide a definitive confirmation regarding whether the baby has Down’s syndrome or other tested chromosomal conditions. If the results indicate a positive outcome (indicating a high chance), additional invasive testing becomes necessary to obtain a conclusive diagnosis. However, it’s essential to understand that any invasive testing carries a slight risk of miscarriage.

Illumina, Inc, an American biotechnology company founded in 1998, specializes in producing high-throughput DNA sequencing systems, commonly called DNA sequencers. They have achieved this position of prominence by building on groundbreaking technology originally developed by the British DNA sequencing company Solexa, based in Cambridge, UK. In a significant move, Illumina acquired Solexa, merging the pioneering DNA analysis capabilities of Solexa with its own expertise.

As of 2021, Illumina commands an impressive 80% share of the global DNA sequencing market, establishing itself as a dominant force in the field. Their commitment to innovation and quality has made them a trusted name in the biotechnology industry.

Illumina’s extensive experience and reputation for producing high-quality equipment extend to noninvasive prenatal testing (NIPT) applications. Their advanced technology plays a pivotal role in ensuring accurate and reliable results in this critical area of healthcare. Our recommended NIPT provider PrenatalSafe based on Illumina’s biotechnology.

For noninvasive prenatal testing (NIPT), Illumina collaborates closely with Hamilton Robotics, enhancing the efficiency and reliability of their technology. This collaboration ensures that Illumina’s advanced sequencing systems, like the VeriSeq NIPT Solution v2, are seamlessly integrated with automated processes provided by Hamilton Robotics. This partnership contributes to the streamlined and high-quality NIPT services that laboratories like Eurofins PrenatalSafe can offer to healthcare professionals and expectant parents.

The Illumina VeriSeq NIPT Solution v2 is a highly advanced and specialized piece of equipment and software developed collaboratively by two prominent American biomedical companies, Illumina and Hamilton Robotics. This technology represents a significant advancement in prenatal testing and is vital in ensuring the accuracy and reliability of noninvasive prenatal testing (NIPT) results.

It’s important to understand that the Illumina VeriSeq NIPT Solution v2 is not a standalone test or a brand name in itself. Instead, it serves as the underlying technology that powers NIPT services provided by various healthcare providers and laboratories. These providers often use their own unique trade names for the tests they offer based on this technology.

For example, Eurofins, a well-established and reputable NIPT provider, has been utilizing the Illumina VeriSeq technology for many years to conduct their NIPT, which they market under the name “PrenatalSafe.” Eurofins’ extensive experience and track record with this equipment have contributed to their reputation.

The VeriSeq NIPT Solution v2 is a complete package for noninvasive prenatal testing (NIPT) using next-generation sequencing (NGS) technology. It includes reagents for DNA extraction, sample preparation, and sequencing. It has an onsite server for secure data storage and analysis and data analysis software capable of generating comprehensive qualitative NIPT results. This automated and reliable system offers rapid turnaround times (26 hours for the cycle), enabling laboratories to process up to 96 samples in approximately one day.

This Illumina NIPT solution provides highly accurate information about fetal chromosomal status as early as 10 weeks of gestation, using just a single maternal blood draw. It offers screening for aneuploidies in all autosomes, chromosomes X & Y, and identifies partial deletions and duplications larger than 7 Mb across the genome. We use this advanced technology in for our SMART TEST. With its high sensitivity and specificity, NGS-based NIPT reduces the need for invasive procedures.

It’s important to note that while the Illumina VeriSeq NIPT Solution v2 is a valuable tool, the accuracy of NIPT tests relies on the laboratory’s expertise and accreditation. Specifically, ISO 15189 accreditation, like that offered by the United Kingdom Accreditation Service (UKAS), is a crucial indicator of quality and reliability.

If a lab has previously struggled with the performance of NIPT tests or lacks accreditation, trust in its results may be questioned. In our evaluation of UK labs using Illumina VeriSeq NIPT Solution v2, PrenatalSafe stands out as a strong choice. Located in the UK, they offer accessibility, accreditation, local expertise, and support in cases of abnormal results, making them a compelling option for accurate and trustworthy NIPT services.

It’s noteworthy that the Illumina VeriSeq NIPT Solution v2 has had such a significant impact on the noninvasive prenatal testing (NIPT) landscape in that it prompted TDL, a long-standing monopolistic provider of Harmony NIPT in the UK, to transition to the technology used by their competitor, Eurofins PrenatalSafe. This move underscores the remarkable capabilities and performance of the VeriSeq NIPT Solution v2.

While TDL may be in the process of adopting this new and advanced technology, it’s reasonable to anticipate that, with time and effort, they may achieve results similar to those demonstrated by Eurofins PrenatalSafe. This transition represents a commitment to providing improved NIPT services and underscores the continuous advancements in the field of prenatal testing.

Expectant parents can look forward to a more competitive landscape in the UK that drives innovation and ultimately benefits patients by offering access to advanced and reliable NIPT options.

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

The 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 a proportion of all positive results. As a practical example, the Prenatalsafe Test has a 99.3% PPV for Down’s Syndrome, meaning that 99.3% of the fetuses identified as ‘High Probability’ will statistically have the condition. However, the limitation of the test is that in 0.7% 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.

There has been confusion about certain aspects of NIPT in the past – please see this notice. If any of the above is still unclear to you, please contact us via email or phone, and our friendly staff 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.

PrenatalSafe uses advanced genomics technology and a proprietary test algorithm. This NIPT offers secure performance for common chromosomal anomalies such as Down’s (trisomy 21), Edwards (trisomy 18), and Patau (trisomy 13) syndromes. The great things about PrenatalSafe are that it needs a small amount of maternal blood (just one tube) and has low no-call rates (less than 2%). PrenatalSafe works in situation of ‘vanished’ twin syndrome where other NIPT options are not applicable. Moreover, it offers a high level of accuracy when it comes to optional determining the gender of the baby.

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 alternative to the Harmony test with only the limitation of limited experience with this test in London.

We offer NIPT for:

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

• fetal sexing  (optional)

The newly established UK lab in Guilford closely mirrors the primary Eurofins Genoma Lab situated in Rome, Italy. It adopts identical equipment, bioinformatics processes, and protocols as the central lab, which is renowned as the foremost NIPT provider in Europe. While the UK Lab’s services have only recently commenced, there is currently no available data concerning its performance. However, there is no compelling rationale to anticipate any variance in performance from the UK Lab.

For reference, kindly find below the statistical analysis provided by Eurofins Genoma, derived from an extensive sample size of 71,883 pregnancies:

For Down’s syndrome (T21):

• Sensitivity 99.54%
• Specificity 100%
• Positive predictive value 99.32%
• Negative predictive value 100%

For Edwards syndrome (T18):

• Sensitivity 100%
• Specificity 100%
• Positive predictive value 98.94%
• Negative predictive value 100%

For Patau’s syndrome (T13):

• Sensitivity 100%
• Specificity 99.99%
• Positive predictive value 82.22%
• Negative predictive value 100%

Our basic PrenatalSafe panel does not include sex chromosome anomalies (SCA) or microdeletions.

For our extended NIPT package, which includes SCA and microdeletions please refer to Smart Test NIPT.

We highly recommend undergoing the NIPT in conjunction with our comprehensive early anomaly scan, the 10 Weeks Scan, at the earliest opportunity – ideally at 10 weeks into your pregnancy. Detecting chromosomal or structural anomalies early provides greater flexibility in managing these conditions throughout your pregnancy. In the event of a sample failure, there’s ample time for a redraw without causing delays.

If you’re uncertain about the exact stage of your pregnancy, we urge you to consider our Viability Scan at around 7-8 weeks. This scan helps determine your pregnancy’s age, enabling us to arrange the earliest possible NIPT appointment for you.

If you choose not to undergo the Viability Scan, please allow a few days after reaching the 10-week mark to prevent the need for repeat appointments for blood collection. Additionally, by coming too early, you might miss out on the benefits of the 10 Weeks Scan, as your baby might be too young for a proper early anomaly assessment.

In theory, NIPT can be conducted from 10 to 40 weeks, but it’s strongly advised to opt for the test in the first trimester. This is because pregnancy management options become limited in the second trimester.

Yes, you can. Panorama AI is the only NIPT that 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 scanning from 9 weeks 4 days.

PrenatalSafe and Harmony do not work at 9 weeks.

The PrenatalSafe Test is not validated and can not be used for use 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)

Please note that all types of IVF pregnancies are eligible for PrenatalSafe Test

Turnaround time of the PrenatalSafe Test in London is fast – about 2-4 working days. It is better than the previously used Harmony Test by TDL.

A specialized medical courier service securely collects the sample from our clinic to Eurofins Lab in Guilford.

The Guilford Lab uses an advanced, fully automated VeriSeq whole-genome sequencing device by Illumina. An efficient workflow allows a sample to report in 26 hours. The dedicated bioinformatics algorithm calculates the probability of chromosomal anomalies and, after validation, the results are sent to us for further reporting to our patients.

After your scan appointment, you will be provided with a comprehensive scan report generated by our medical experts. This report will be available in both printed format and as a PDF, delivered securely through our cloud platform, Tricefy.

Upon receiving the NIPT test results from the lab, our clinicians will review and authorize them. Following this review, a member of our approachable clinical team will reach out to you over the phone to explain the implications of the test results. Subsequently, we will share an electronic version of the results with you via Tricefy for your reference.

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 with any screening test NIPT has some disadvantages.

Here there are the most significant NIPT limitations:

• relatively high cost of the cfDNA tests
• whilst a very sensitive screening test, it is not diagnostic
• cannot detect ANY physical (structural) anomaly
• limited effectiveness for babies that have increased nuchal translucency (NT) thickness or physical (structural) anomaly
• failure to return a result in up to 6.5% of women (‘no-call’ results), which is more common for Harmony Test

The Harmony test, an essential non-invasive prenatal screening for common chromosomal syndromes, has garnered a reputation as the first NIPT option introduced in London over a decade ago. Despite its demonstrated accuracy in detecting Down syndrome, it is crucial to underscore its significant drawbacks.

Notably, the test exhibits a high rate of inconclusive results, with a failure rate of 6.5%, according to our internal audit conducted between 2022 and 2023. This failure rate is particularly pronounced when the test is performed early in pregnancy.

The statistical performance metrics of the Harmony Test fall short when compared to the more advanced tests of the new generation, such as PrenatalSafe or Panorama tests.

In conclusion, the Harmony test’s reputation for reliability is overshadowed by its substantial shortcomings.

In the current landscape, more advanced and superior NIPT options are available in London and the UK. All our other NIPT options: PrenatalSafe, Panorama Test, and UNITY, perform better.

Our team of experts is dedicated to guiding you through this decision-making process and recommending the most optimal NIPT option tailored to your individual circumstances.

The PrenatalSafe NIPT offers several distinct advantages when compared to other NIPT providers:

• Uses cutting-edge technology
• Provides reliable Down’s syndrome screening
• Requires a minimal amount of maternal blood
• Provides rapid results
• Exhibits low rates of inconclusive outcomes
• Serves as a superior alternative to the Harmony Test
• Applicable even in cases of vanishing twin syndrome
• Holds a strong reputation in Europe

But, to keep it accurate, here’s a little thing to consider:

• Limited experience using the test in London

In case the NIPT result is 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 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 the PrenatalSafe Test is very accurate, around 0.7% (data of Eurofins Genoma) 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 <2% of cases, we will need to contact you without giving you a test result and ask to come 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 additional blood test.

It is because, in a small proportion of blood specimens submitted after 10 weeks gestation, there is an insufficient amount of the baby’s cfDNA. This situation is called a low fetal fraction. The chance of having a low fetal fraction gets higher with increased maternal body weight. There are other rare factors making NITP results inconclusive.

In the case of PrenatalSafe Test no-call results on repeated samples (0.5% probability), 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  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 to wait 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 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 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.

Yes, PrenatalSafe or UNITY only.

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 vanishing twin phenomenon is complicated due to contamination of the sample by DNA of non developing twin pregnancy. Both Harmony and Panorama NIPT cannot be used this situation.

However, we have a specific solution for pregnancies affected by this rare condition: PrenatalSafe Test, which can be used in the cases of vanishing twin phenomenon. Please get in touch to enquire.