KNOVA

Non-Invasive Prenatal Testing (NIPT), also known as Non-Invasive Prenatal Screening (NIPS), serves to evaluate the likelihood of conditions such as Down’s syndrome or other chromosomal and single gene disorders in unborn babies. NIPT analyses small DNA fragments from the baby’s placenta, known as ‘cell-free DNA’ or ‘cfDNA’, which circulate in the bloodstream of pregnant mothers. This placental cfDNA generally mirrors the baby’s DNA, allowing early identification of certain chromosomal anomalies without any risk to the baby.

It’s crucial to understand that NIPT is a screening test, meaning it does not confirm whether the baby has Down’s syndrome or other chromosomal conditions. Should the results show a high chance, further invasive testing is required for a definitive diagnosis. However, bear in mind that such invasive testing carries a slight risk of miscarriage.

According to data from Fulgent, in a study involving over 1000 high-risk pregnancies, KNOVA achieved a 98.5% sensitivity rate and a 99.3% specificity rate. This performance compares favorably to standard diagnostic tests, both prenatal invasive and postnatal, for the multiple conditions screened—not just Down’s syndrome.

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

We cannot specify precisely, as it remains a company commercial secret. However, we believe that Fulgent, a highly renowned genomic company with the capability to examine over 18,000 human genes, is confident that integrating their microdeletions and monogenic screening platforms will significantly boost NIPT’s performance. Fulgent possesses advanced genetic tools essential for developing and implementing this test. Their preliminary data indicate that including targeted monogenic conditions alongside chromosomal abnormalities (aneuploidies and microdeletions) resulted in a 60.7% increase in the detection rate.

KNOVA screens for 5 types of chromosomal syndromes associated with severe health/mental conditions or possible fetal demise:

1. Trisomy 21 – Down syndrome
2. Trisomy 18 – Edwards syndrome
3. Trisomy 13 – Patau syndrome
4. Trisomy 15
5. Trisomy 16
6. Trisomy 22

KNOVA screens for 12 chromosomal microdeletions associated with severe health/mental conditions:

1. 1p36 del-  1p36 deletion syndrome
2. 2q33 del – 2q33.1 deletion syndrome
3. 4p16 del – Wolf-Hirschhorn syndrome
4. 5p15 del – Cri-du-Chat syndrome
5. 8q23q24 del – Langer-Giedion syndrome
6. 9p del – 9p deletion syndrome
7. 11q23q25 del – Jacobsen syndrome
8. 15q11.2-q13 del – Prader-Willi syndrome / Angelman syndrome
9. 17p11.2 del – Smith-Magenis syndrome
10. 18p del – 18p deletion syndrome
11. 18q22q23 del – 18q deletion syndrome
12. 22q11.2 del – 22q11.2 deletion syndrome (DiGeorge syndrome)

KNOVA screens for 56 genes associated with 30+ monogenic conditions. Among them are:

• Noonan syndrome
• Noonan spectrum disorders (RASOpathies)
• Skeletal dysplasias
• Craniosynostoses
• CHARGE syndrome
• Cornella de Lange syndrome
• Tuberous sclerosis complex
• Sotos syndrome 
• and many others

We strongly recommend undertaking the NIPT alongside our comprehensive early anomaly scan, the 10 Weeks Scan, as soon as possible—ideally at 10 weeks into your pregnancy. Early detection of chromosomal or structural anomalies offers greater flexibility in managing these conditions throughout your pregnancy. Should there be a sample failure, there is sufficient time for a redraw without any delays.

If you are unsure about the exact stage of your pregnancy, we recommend our Viability Scan at around 7-8 weeks. This scan determines the age of your pregnancy, enabling us to schedule your NIPT at the earliest opportunity.

If you decide against the Viability Scan, please wait a few days after reaching the 10-week mark to avoid the need for repeat blood collection appointments. Coming too early may also mean missing out on the full benefits of the 10 Weeks Scan if your baby is too young for a thorough early anomaly assessment.

While NIPT can technically be conducted from 10 to 40 weeks, we strongly advise opting for the test in the first trimester. Management options for pregnancy become more limited as the second trimester progresses.

The KNOVA Prenatal Cell-Free DNA Screening has not been validated for use in pregnancies involving:

• a history of or active malignancy
• IVF pregnancies using an egg donor
• a pregnancy with twins, triplets, quadruplets or higher-order
• vanishing twin syndrome
• a history of bone marrow or organ transplants
• mosaicism for the parents
• maternal aneuploidy (chromosomal abnormality), microdeletion or single-gene disorder

After your scan, our medical experts will provide you with a detailed scan report in both printed form and as a PDF, securely delivered through our cloud platform, Tricefy.

Once we receive the NIPT test results from the laboratory, our clinicians will review and authorize them. Following this, a member of our friendly clinical team will contact you by phone to discuss the implications of your results. We will then send you an electronic version of the results via Tricefy for your reference.

KNOVA is not a diagnostic tool and should not be used as the sole basis for making decisions about your pregnancy. It is designed to identify if your pregnancy has a higher-than-average risk of a severe disorder, allowing you the option to consider further diagnostic testing if needed. As KNOVA is a non-invasive test, it presents a relatively low risk and serves as an excellent initial screening option.

Should the NIPT indicate a high chance of Down syndrome or another condition, our doctor will contact you to explain the recommended next steps. Typically, high-risk results require confirmation through diagnostic tests, such as CVS (Chorionic Villus Sampling) or amniocentesis.

Our medical and administrative teams are committed to supporting you through challenging times. They will do everything possible to facilitate smooth and prompt arrangements for further genetic counselling and diagnostic procedures, should they be necessary.

No, KNOVA NIPT is not suitable in cases of vanishing twin syndrome.

Vanishing twin syndrome occurs in twin pregnancies when one embryo or fetus does not develop or perishes early in pregnancy. This condition complicates NIPT interpretation due to DNA contamination from the non-developing twin. Similarly, Panorama NIPT is unsuitable under these circumstances.

However, we offer a specific solution for pregnancies impacted by this rare condition: the PrenatalSafe Test, designed to be effective in cases of vanishing twin syndrome. Please contact us to learn more.

Validation study for KNOVA Prenatal Cell-Free
DNA Screening (NIPT/NIPS) was published in Nature.

Zhang J, et al. Prospective prenatal cell-free DNA screening for genetic conditions of heterogenous etiologies. Nat Med. 2024 Feb;30(2):470-479.

Abstract:

Prenatal cell-free DNA (cfDNA) screening uses extracellular fetal DNA circulating in the peripheral blood of pregnant women to detect prevalent fetal chromosomal anomalies. However, numerous severe conditions with underlying single-gene defects are not included in current prenatal cfDNA screening. In this prospective, multicenter and observational study, pregnant women at elevated risk for fetal genetic conditions were enrolled for a cfDNA screening test based on coordinative allele-aware target enrichment sequencing. This test encompasses the following three of the most frequent pathogenic genetic variations: aneuploidies, microdeletions and monogenic variants. The cfDNA screening results were compared to invasive prenatal or postnatal diagnostic test results for 1,090 qualified participants.

The comprehensive cfDNA screening detected a genetic alteration in 135 pregnancies with 98.5% sensitivity and 99.3% specificity relative to standard diagnostics. Of 876 fetuses with suspected structural anomalies on ultrasound examination, comprehensive cfDNA screening identified 55 (56.1%) aneuploidies, 6 (6.1%) microdeletions and 37 (37.8%) single-gene pathogenic variants. The inclusion of targeted monogenic conditions alongside chromosomal aberrations led to a 60.7% increase (from 61 to 98) in the detection rate. Overall, these data provide preliminary evidence that a comprehensive cfDNA screening test can accurately identify fetal pathogenic variants at both the chromosome and single-gene levels in high-risk pregnancies through a noninvasive approach, which has the potential to improve prenatal evaluation of fetal risks for severe genetic conditions arising from heterogenous molecular etiologies.

KNOVA is not a diagnostic tool and should not solely guide decisions about your pregnancy. It is designed to detect if there is a higher-than-average risk of a severe disorder, offering you the possibility of further diagnostic testing. While the data from invasive tests like CVS or amniocentesis are generally more conclusive, these tests often do not assess for monogenic disorders associated with increased nuchal translucency (NT), such as Noonan syndrome, Kabuki syndrome, and Thanatophoric dysplasia. An exome analysis would be required, and the NHS has stringent criteria for such tests, which generally do not apply merely for increased NT. In our view, KNOVA is the NIPT of choice in cases of increased NT, providing a valuable screening option when detailed diagnostic testing may not be feasible.

Please contact us if you would like more information regarding NIPT options for fetuses with increased NT.