
The Sage™ Prenatal Screen is a non-invasive prenatal screening solution to estimate the risk of a fetus having Trisomy 21, Trisomy 18, Trisomy 13, Rare Autosomal Aneuploidies (RAA), Sex Chromosome Aneuploidies (SCA) and the most clinically relevant microdeletions.
Sage™ Prenatal Screen
The Sage™ Prenatal Screen is a Safe, Accurate, Genetic Evaluation of placental DNA in maternal blood using Next Generation Sequencing technology, to estimate the risk of a fetus having Trisomy 21, Trisomy 18, Trisomy 13, Rare Autosomal Aneuploidies (RAA), Sex Chromosome Aneuploidies (SCA) and the most clinically relevant microdeletions.
Sage™ Prenatal Screen has a menu-based approach to cell-free DNA (cfDNA) screening, where upon consultation with the pregnant mother, the healthcare professional can select which chromosome disorders to screen for and can customise it for each patient depending on their background, maternal history and wishes. The Sage™ Prenatal Screen can deliver results from 3 to 5 days.

Autosomal Aneuploidies
The Sage™ Prenatal Screen estimates the risk of a fetus having Down’s syndrome (Trisomy 21), Edwards’ syndrome (Trisomy 18) and Patau’s syndrome (Trisomy 13). In addition, a genome-wide aneuploidy detection analysis on the remaining chromosomes can be carried out and reported.
Sex Chromosome Aneuploidies
Upon request, the following sex chromosome aneuploidies can be screened for:
Monosomy X
Turner syndrome
Monosomy X
seen in about 1 in 2,000 live female births
XXX
Triple X syndrome
XXX
seen in about 1 in 900-1,000 live female births
XXY
Klinefelter syndrome
XXY
seen in about 1 in 500-1,000 live male births
XYY
Jacobs syndrome
XYY
seen in about 1 in 1,000 live male births
Microdeletions
Microdeletion syndrome is caused by the absence of a small portion of genetic material in the chromosome. They can vary greatly in severity, with the symptoms of microdeletions ranging from minimal developmental delays to sever anomalies e.g. cardiac defects, neurological malformations etc.

Upon request, the following rare microdeletions can be screened for:
DiGeorge syndrome (22q11.2 deletion)
1p36 deletion syndrome
Prader-Willi syndrome (15q11.2-q13 deletion)
Angelman syndrome (15q11.2-q13 deletion)
Cri-du-Chat syndrome (5p15 deletion)
Wolf-Hirschhorn syndrome
Fetal Sex Determination

Upon request, the fetal sex can be determined with >99% accuracy.
Fetal Fraction
The Sage™ Prenatal Screen analyses and reports the amount of placental cfDNA circulating in the maternal blood stream and reports this as fetal fraction. Some pregnant women may have too little fetal (placental) DNA available for analysis which is reported as "low fetal fraction". There may be several reasons for this; for instance, women with a high maternal weight may have increased blood volume which could result in a dilution of the cell-free placental DNA in the maternal plasma.
The Sage™ Prenatal Screen incorporates clever bioinformatics software that is able to produce valid and accurate results in samples that have as little as 3.5% fetal fraction.
Yourgene provides safe and accurate NIPT screening solutions across multiple platforms, enabling us to meet your laboratory’s testing needs. We have two Sage™ NIPT workflows, Sage™ 12 NIPT workflow or Sage™ 32 NIPT Workflow, depending on your requirements, facilitating a more efficient workflow and improved performance, saving you time and money.
Please note that Sage™ Prenatal Screen is not available for sale in the United States.
Sage™ Prenatal Screen
The Sage™ Prenatal Screen is a simple, fast process that can be run by any trained technician. The Sage™ 12 NIPT Workflow is ideal for low to medium volume sample throughput laboratories, enabling laboratories to build up volumes and then transition seamlessly onto the Sage™ 32 NIPT Workflow to meet the rising demand for testing.
The Sage™ 12 NIPT Workflow is a manual, low cost, flexible solution for core trisomy screening, which enables 12 samples to be run simultaneously. As demand rises this workflow is easily scalable to the Sage™ 32 NIPT Workflow which offers both manual and automated options, increasing flexibility, scalability and sequencing efficiencies.
The Sage™ 32 NIPT Workflow enables 32 samples to be processed in one sequencing chip and utilises the Yourgene® QS250, powered by Ranger® Technology. Ranger® Technology allows automated high-throughput target enrichment of cfDNA NGS library constructs prior to sequencing, enabling great improvements in fetal fraction enrichment.
In NIPT, Ranger® Technology next generation size selection and enrichment enables labs to get the results they are looking for first time, reducing failure rates and improving precision, enabling more pregnant mothers to receive a safe, fast and accurate screening result.
In addition to next generation size selection, the Yourgene® QS250 also allows fragment analysis and solution-based fluorescence quantification assays with a single piece of equipment, giving greater cost efficiencies for the laboratory.
Both Sage™ Workflows run on the Ion Torrent sequencing system from Thermo Fisher Scientific.
Cloud-based NIPT analysis

The Sage™ analysis uses Sage™ Link which is a cloud-based bioinformatics portal. The resulting data is processed so that a small data file can be easily, quickly and safely uploaded to Sage™ Link. After a brief time, individual patient reports are ready for download. Each report is easy to follow and is signed by the laboratory once it is finalised.
Performance
The performance of the Sage™ Prenatal Screen is assessed by collecting data from laboratories and clinics using the Sage™ 32 or Sage™ 12 NIPT Workflows to screen for trisomy 21, trisomy 18, trisomy 13, Rare Autosomal Aneuploidies (RAA), Sex Chromosome Aneuploidies (SCA) and the most clinically relevant microdeletions.

Sage™ 12 NIPT Workflow performance observed following global post-market surveillance on 15,762 samples:
(152)
(152 / 155)
95%CI: 94.45-99.60
(15607 / 15607)
95%CI: 99.98-100%
(53)
(53 / 53)
95%CI: 93.28-100%
(15706 / 15709)
95%CI: 99.94-100%
(26)
(26 / 26)
95% CI: 86.77-100%
(15734 / 15736)
95%CI: 99.95-100%
(122)
(122 / 125)
95% CI: 93.15-99.5%
(15633 / 15637)
95%CI: 99.93-99.99%
(50)
(50 / 50)
95%CI: 92.89-100%
(15710 / 15712)
95% CI: 99.95-100%)
(6)
95%CI: 42.13-99.64%
(4184 / 4185)
95%CI: 99.91-100%
(7473)
99.99%

Sage™ 32 NIPT Workflow performance observed following global post-market surveillance on 70,186 samples (singleton pregnancies):
(1098)
(1098/1099)
95% CI: 99.49-100%
(15607 / 15607)
95%CI: 99.98-100%
(172)
(172/173)
95% CI: 96.82-99.99%
(15706 / 15709)
95%CI: 99.94-100%
(1166)
(116/116)
95% CI: 96.87-100%
(15734 / 15736)
95%CI: 99.95-100%
(529)
(529/530)
95% CI: 99.31-100%
(15633 / 15637)
95%CI: 99.93-99.99%
(185)
(185/185)
95% CI: 98.03-100%
(15710 / 15712)
95% CI: 99.95-100%)
(3)
(3/3)
95% CI: 29.24-100%
(4184 / 4185)
95%CI: 99.91-100%
(39177)
>99.99%

Sage™ 32 NIPT Workflow performance observed following global post-market surveillance on 1,776 samples (twin pregnancies):
(22)
(22/22)
(1754/1754)
(1)
(1/1)
(1775/1775)
(3)
(3/3)
(1773/1773)
(17)
(17/17)
(1759/1759)
(4)
(4/4)
(1772/1772)
Please note that all performance is dependent on laboratories reporting their discordant results to Yourgene Health. The number of samples screened for microdeletions is lower than for the other trisomies, SCAs or AAs. From data held on file by Yourgene Health Plc, correct at time of publishing (31st October 2022).

Using the MagBench™ cfDNA Extraction Solution for Sage™ NIPT Workflow from Yourgene Health
In this edition of Your Expert, Yourgene Health interviewed Hanchiang Chin (HC) & You-Hsuan Lin (YHL), two superusers from within our Taipei laboratory on their thoughts and experiences using Yourgene Health’s MagBench™ cfDNA Extraction Solution to understand the key benefits of the system when used in combination with Non Invasive Prenatal Testing (NIPT) Workflows.
The Truth About Statistics in NIPT
Non-invasive prenatal testing (NIPT) is a relatively new tool in prenatal care, helping clinicians to assess the chance of fetal chromosomal abnormalities early in a pregnancy. It is more accurate than traditional screening techniques for common fetal aneuploidies – Down’s syndrome, Patau’s syndrome, and Edwards’ syndrome – and carries no associated miscarriage risk.

"The partnership between Yourgene Health and the six NHS hospitals that took part in the study worked really well. The research teams were hardworking, passionate and dedicated to the study and has led to a great piece of research. They were a joy to work with and we look forward to the opportunity to collaborate again in the future."
View the full Your Comment articles below
NIPT for Sex Chromosome Aneuploidies and Autosomal Aneuploidies. A Q&A with Dr Greg Fitzgibbon - 26 May 2021
NIPT for Sex Chromosome Aneuploidies and Autosomal Aneuploidies. A Q&A with Dr Greg Fitzgibbon – 26 May 2021
Yourgene Health has recently launched IONA®Care, an advanced prenatal screening test that performs whole-genome analysis to measure the likelihood that a pregnant woman is carrying a fetus with one the most common trisomies (trisomy 21, 18 and 13), any other Autosomal Aneuploidy (AA) or a Sex Chromosome Aneuploidy (SCA). IONA® Care is available from the Yourgene Genomic Services laboratory in Manchester, UK. The test is available as a menu, enabling pregnant women, their families and clinicians to only find out information on the conditions specifically requested. Yourgene felt this was the responsible thing to do as screening for AAs and SCAs and the follow-up counselling can be more complicated than the more common trisomies and therefore felt this additional information should be optional. We spoke with Dr Greg Fitzgibbon, our Director of Clinical Affairs, to find out more about screening for AAs and SCAs and the clinical implications and benefits.
Dr Greg Fitzgibbon, PhD, DipRCPath, HCPC – Director of Clinical Affairs
Greg is a Clinical Laboratory Director with New York State Department of Health Certificate of Qualification and provides the clinical expertise required for Yourgene Health’s expanding business and product portfolio. Greg previously lead the operations team in performing product development, as well as ensuring the compliance to regulatory requirements and performing business management activities.
Greg holds a Doctorate in Molecular Biology, he is a Diplomate of the Royal College of Pathologists and has over 8 years management experience in Clinical Science for the NHS. He also has over 8 years involvement with the inception, growth and development of Biotechnology businesses including Syngenta, Gen-Probe, Hologic and Epistem on top of validating technologies for corporate giants including GSK and Government Institutions.
When thinking about testing for SCAs and AAs, are there particular groups of women who are at a higher risk of having a baby that is affected by one of the conditions? For example, we know that the risk of having a baby affected by Down’s syndrome increases with maternal age; is the same true for these other conditions and are there other factors that affect the incidence?
Yes, like Down’s syndrome SCAs and AAs are aneuploidy syndromes and therefore the incidences of certain SCAs and AAs increase as maternal age increases. This is caused due to an erroneous event called nondisjunction, essentially a failure of homologous chromosome to separate within the egg, which occurs more frequently with advanced maternal age. I say ‘certain’ SCAs however because in the case of Turner Syndrome (monosomy X) there is much higher incidence of sperm production errors therefore the majority of cases of Turners are paternal in origin.
What are the clinical benefits of testing for SCAs and AAs?
For SCAs, the main clinical benefit is earlier detection of the conditions. Unlike Down’s syndrome and the more common autosomal trisomies, SCAs can sometimes have quite subtle features on ultrasound scans which can make them more difficult to detect prenatally. Consequently, a large proportion of cases, particularly Klinefelter’s syndrome (47,XXY) are identified and diagnosed either postnatally, at puberty, or even later on in life (if at all). Routine SCA screening using NIPT allows for the detection of these conditions prenatally from 10 weeks gestational and at no risk to the fetus. This approach not only provides parents with insight, but facilitates improved care by allowing clinical teams to arrange patient care and obstetric management as appropriate.
For AAs there is the opportunity for improved patient management by providing information around recurrence risks. The vast majority of AA cases are not viable and unfortunately will often end in miscarriage. In these cases, the identification of AAs offers clinical benefit as it has determined that the cause is not hereditary, but is in fact a random (nondisjunction) event and therefore recurrence is less likely in subsequent pregnancies.
Should a result come back as high risk, what would the recommended next step be? What would the clinical pathway be?
Testing approaches can vary depending on the testing laboratory and local regulations but the next steps in the testing pathway should always be to discuss the results carefully with the clinician/genetic counsellor in consideration with the patient’s medical background, preferences, test limitations, positive predictive values for the conditions and the need for further confirmatory testing. NIPT is a screening test, not diagnostic; it is recommended that high-risk results be confirmed using diagnostic methods. This may well require invasive sampling either by chorionic villus sampling (CVS) or amniocentesis in order to karyotype the fetus using either cytogenetic or molecular methods (or both).
If the invasive testing confirms the screening result a general clinical pathway would be a consultation where a clinician would speak to the parent(s) and would explain the findings, provide them with sufficient information so that they can make an informed choice regarding their next steps.
How does this test compare to the current pathway for identifying babies affected by these conditions?
The current testing pathway requires invasive sampling of placental or fetal cells by CVS or amniocentesis respectively. CVS is taken at around 10-13 weeks and amniocentesis at around 14-18 weeks gestation, whereas NIPT can be taken as early as 10 weeks gestation. The invasive sampling methods do have the added benefit of being used in diagnostic testing as opposed to screening testing but there is a risk of miscarriage of up to 2% for CVS and 1% for amniocentesis sampling which is negated by the NIPT approach. NIPT only requires a small blood sample from the mother which present no risk to the fetus. If the invasive samples are used for cytogenetic investigations, they will require cell culture with expected reporting times of up to 14 days. Molecular applications including QF-PCR can however provide preliminary results in less than 24 hours.
What support is available for families should they get a high risk result and subsequently confirmed via a diagnostic procedure?
There are several support organisations for families and families would be signposted by their healthcare providers. Antenatal Results and Choices (ARC) offer non-directive individualised information and support to parents. We have included some support organisations below, please note this list is not exhaustive and is provided for information only. Inclusion on this list does not indicate an endorsement by Yourgene Health and Yourgene accept no responsibility for the content of external websites.
- Unique – Support for Rare Chromosome Disorders
https://rarechromo.org/ - The Klinefelter’s Syndrome Association (KSA) (UK)
https://www.ksa-uk.net/ - XYY Syndrome (for Parents) – Nemours KidsHealth
https://kidshealth.org/en/parents/xyy-syndrome.html - Turner Syndrome Support Society
https://tss.org.uk/
Videos
The MagBench™ cfDNA Extraction Solution for Sage™ NIPT Workflow
Sage™ 32 NIPT Workflow
Sample reports

A sample trisomy Sage™ prenatal test screening report

A sample SCA Sage™ prenatal test screening report

A sample microdeletions Sage™ prenatal test screening report
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