Illumiscreen Non-Invasive Prenatal Screening – Important Information

Illumiscreen Non-Invasive Prenatal Screening

Limitations of the test

This test is designed to screen for chromosome aneuploidies and is validated for chromosomes 21, 18, 13 and for fetal gender. The test is validated for singleton and twin pregnancies with gestational age of at least 10 weeks 0 days, as estimated by last menstrual period, crown rump length, or other appropriate method (equivalent to 8 weeks fetal age as determined by date of conception).

This is a screening test with a risk of false positive or false negative results. A negative test result does not eliminate
the possibility of chromosomal abnormalities such as trisomy 21, trisomy 18, trisomy 13, Monosomy X, XXX, XXY and XYY. For confirmatory diagnosis, invasive testing such as chorionic venous sampling and amniocentesis is required.

This test does not cover other genetic conditions including but not limited to chromosomal abnormalities other than the chromosomes stated above, subchromosomal abnormalities, triploidy, single gene disorders, birth defects such as open neural tube defects or other congenital conditions.

When an aneuploidy detected result is reported in a twin pregnancy, the status of each individual fetus cannot
be determined. Although the presence or absence of Y chromosome material can be reported in a twin pregnancy, the occurrence of sex chromosome aneuploidies such as MX, XXX, XXY and XYY cannot be evaluated in twin pregnancies.

There is a small possibility that the test results might not reflect the chromosomes of the fetus, but may reflect chromosomal changes of the placenta (confined placental mosaicism) or of the mother (chromosomal mosaicism).

Test Performance

Test Method

Illumiscreen is performed using massively parallel sequencing at Labtests Auckland. The whole genome sequencing is performed using circulating cell-free DNA extracted from maternal plasma to determine the copy number of chromosome 13, 18, 21 and sex chromosomes. DNA libraries are prepared using Illumina TruSeq Nano DNA Library Prep kits and next generation sequencing is performed in NextSeq 500. The data is analysed by the proprietary algorithm SAFeRTM.

COVID Can’t Stop Us

Learn how we assisted with the COVID-19 testing capacity with the Ministry of Health.

Covid can’t
stop us

On 18th March 2020 the Illumiscreen team at Labtests and other Healthscope (now APHG) laboratories across New Zealand were working alongside the Ministry of Health to establish COVID-19 testing capacity ahead of what was expected to be a pandemic that would require a well-coordinated national approach.

Labtests had to call on their expert molecular staff that are most typically work in the laboratory dedicated to Illumiscreen testing, our non-invasive prenatal testing service (NIPT). NIPT samples are sent from all over the country are processed by our laboratory in Auckland, any disruption to this service impacts expectant parents
across New Zealand.

As internal conversations were happening in the laboratory it became clear that our amazing molecular staff would have to be redeployed to set up the COVID-19 testing platforms with the capacity to process more than 2,700 tests per day at the peak and the ability to significantly increase this when surge capacity was required.

We considered whether we could continue to offer a reliable and sustainable Illumiscreen service while also managing COVID-19
testing and the ask was simply too great. We certainly did not want to introduce pressure on staff and processes that would compromise quality and so this option was quickly eliminated.

Beyond this we explored a range of alternatives including the possibility of sending all samples to the US for testing, however while we were advancing these discussions air transport between
New Zealand and US began reducing day by day. As the blood samples for NIP Tare not stable for more than five days, the inability to predict how long the samples would take to reach their destination meant that we could not progress this further.

By the 24th March we had exhausted all options and made the difficult decision to suspend the service without the ability to predict when we would be able to offer the valuable service to our customers once again.

Through the efforts of our incredible Molecular staff, Labtests reported the first run of Covid-19 tests on 31st March. By late April, as COVID-19 testing was well established, with increased staff headcount and the new molecular staff training in the process of NIPT, we were in a position to consider the earliest possibility of restarting the Illumiscreen service.

Many conversations took place over the weeks that ensued as we worked through a range of scenarios to ensure that staffing levels would be sufficient to continuously and consistently deliver both Illumiscreen testing AND Covid-19 testing, not just at the known current test levels but in the anticipated event of a volume surge.

The incredible molecular team, led by Blair Shilton, developed a number of creative solutions and with suitable options on the table we agreed on a tentative date of 28th May for the Illumiscreen service to re-commence. Before this could become a reality Blair needed to ensure engineers were available to carry out routine maintenance on the laboratory instrument used for the testing, this is essential should if an instrument has been “in hibernation” for any period of time to ensure its reliability.

Meanwhile, our Illumiscreen service specialist Karen Buchan was keeping track of the many customer enquiries asking when the service would be available. She was checking in with the molecular team on a daily basis in a desperate attempt to provide customers with answers!

We waited anxiously to hear if all the relevant technical steps could be successfully completed in time for the hopeful re-opening of the service on 28th May. Just before crunch time we received the thumbs up from Blair: everything was good to go! With that being said there was just one last step – tell our incredible NIPT customers that we’re back in business!

When Auckland entered Level 3 on 12th August the anticipated Covid-19 surge became a reality and with it the pressure on our molecular services.

Our tremendous laboratory team, set up since the country first went into lockdown, had well developed processes for delivering high volume COVID-19 testing including pooling samples, which is a process that allows nucleic acid extraction of multiple samples to be pooled together into a single sample test. Additionally the molecular team had worked diligently to complete cross training of staff which has provided the much needed flexibility and resourcing to ensure consistent and reliable delivery of both COVID-19 AND
Illumiscreen testing.

We are so grateful to our amazing customers for waiting patiently while we aimed to balance two incredibly important priorities at the same time. We are thankful to be delivering peace of mind by way of this clinically-led service to the many expectant parents
who are going through.

NIPT: cost effective, first line screening for all pregnant women

The Illumiscreen prenatal test maximises cost-effectiveness with the lowest failure rate.

NIPT: cost effective, first line screening for all pregnant women

Prior to 2011, prenatal aneuploidy screening options for trisomy 21 included measurement of serum markers and/or sonographic evaluation of the fetus.

1,2 These tests could also report a risk for trisomy 18.

1 The introduction of cell-free DNA (cfDNA)-based noninvasive prenatal testing (NIPT) created a new screening option and facilitated screening for a greater range of fetal aneuploidies (trisomies 21, 18, 13, and sex chromosome aneuploidies).

3 NIPT is now endorsed as a screening option for all pregnant women.

1,4,5. Although NIPT is more expensive than serum screening, it is actually cost effective, as shown below.

Finding the most cost effective solution

While NIPT is an endorsed screening option, 1,4,5 professional societies recommend that diagnostic testing be done following any positive or failed screening test for confirmation.

6,7 Although these invasive diagnostic tests are necessary to confirm results, they’re expensive.

8-10 Therefore, false positive rates (FPR), technical failure rates, and the costs associated with invasive confirmation procedures need to be considered in cost modelling. Compared with a trisomy 21 FPR of around 5% with conventional screening approaches, 11-14 NIPT has a FPR of around 0.1%. 15

The illumiscreen prenatal test maximises cost-effectiveness with the lowest failure rate

Of all the NIPT, the Illumiscreen prenatal tests offer the lowest reported technical failure rate 16-20 substantially reducing additional costs associated with technical failures.

21 The failure rate of 0.1% is 10-fold less than that of other NIPTs on the market.

NIPT and serum screening: Impact of false positive rates and test failures on the number and cost of invasive procedures for unaffected pregnancies. Theoretical example of the number of invasive procedures, and the associated total cost, for serum screening and for commercial NIPTs currently available in the US. Based on published cost estimates for invasive testing 8-10 and published failure rates.16-20

‡ Affected pregnancies with a screening test failure were excluded from the number of detected T21. ‡ Assay failure rate for the Harmony test is based on next-generation sequencing studies and may not be consistent with actual test results achieved using the array- based Harmony test currently in use (published clinical experience data not available).

1. Practice Bulletin No. 163: Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127(5):979-981.
2. WaldNJ,RodeckC,HackshawAK,
WaltersJ,ChittyL,MackinsonAM.First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen. 2003;10(2):56-104.
3. BianchiDW,PlattLD,GoldbergJD,
AbuhamadAZ,SehnertAJ,RavaRP.Genome- wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. 2012;119(5):890-901.
4. GreggAR,SkotkoBG,BenkendorfJL,etal.
Noninvasiveprenatalscreeningfor fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;doi: 10.1038/gim.2016.97.
5. BennP,BorrellA,ChiuRW,etal.
PositionstatementfromtheChromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn. 2015;35(8):725-734.
6. CommitteeOpinionNo.640:Cell-freeDNAScreeningforFetalAneuploidy.Obstet Gynecol. 2015;126(3):e31-37.
7. NationalSocietyofGeneticCounselors.
Abnormalnon-invasiveprenataltesting results: What do they mean? 2015; prenatal-testing-results. Accessed February 25, 2015.
8. BennP,CurnowKJ,ChapmanS,
MichalopoulosSN,HornbergerJ,RabinowitzM. An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population. PLoS One. 2015;10(7):e0132313.
9. FairbrotherG,BurigoJ,SharonT,SongK.
Prenatalscreeningforfetalaneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis.J Matern Fetal Neonatal Med. 2016;29(7):1160-1164.
10. Walker BS, Nelson RE, Jackson BR, Grenache DG, Ashwood ER, Schmidt RL. A Cost-Effectiveness Analysis of First Trimester Non-Invasive Prenatal Screening For Fetal Trisomies in the United States. PLoS One. 2015;10(7):e0131402.
11. Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down’s syndrome. N Engl J Med. 2005;353(19):2001-2011.
12. Norton ME, Baer RJ, Wapner JR, Kuppermann M, Jelliffe -Pawlowski LL, Currier RJ. Cell-free DNA vs sequential screening for the detection of fetal chromosomal abnormalities.
Am J Obstet Gynecol. 2015.
13. Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidyscreening. NEnglJMed.2014;370(9):799-808.
14. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011;31(1):7-15.
15. Gil MM, Quezada MS, Revello R, Akolekar R, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2015;45(3):249-266.
16. Taneja PA, Snyder HL, de Feo E, et al. Noninvasive prenatal testing in the general obstetric population:clinical performance and counseling considerations in over 85,000 cases. Prenat Diagn. 2016;36(3):237-243.
17. Yaron Y. The implications of non-invasive prenatal testing failures: a review of an under discussed phenomenon.PrenatDiagn. 2016;36(5):391-396.
18. McCullough RM, Almasri EA, Guan X, et al. Non-invasive prenatal chromosomal aneuploidy testing–clinical experience: 100,000 clinical samples. PLoS One. 2014;9(10):e109173.
19. Ryan A, Hunkapiller N, Banjevic M, et al. Validation of an Enhanced Version of a Single-Nucleotide Polymorphism-Based Noninvasive Prenatal Testfor Detectionof Fetal Aneuploidies. Fetal Diagn Ther. 2016;doi:10.1159/000442931.
20.Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA Analysis for Noninvasive Examination of Trisomy. NEnglJMed.2015;372(17):1589-1597.
21. Gekas J, Rodrigue M, Nshimyumukiza L, Reinharz D. Failure Rate May Impact Significantly Costeffectiveness of the Technology Used in Down Syndrome Noninvasive Prenatal Screening Programs(Abstract641). Posterpresentedat ACMG Annual Clinical Genetics Meeting; 2016; Tampa, FL22.Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A. SURUSS in perspective. Semin Perinatol. 2005;29(4):225-235.

Highlights From ACOG-SMFM

What is new in DNA screening?

Highlights From ACOG-SMFM

The American Congress of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) issued a joint Practice Bulletin on screening for aneuploidy (PB #163) in May 2016. This bulletin reviews current information for fetal aneuploidy screening options. PB #163 replaces the previous PB #77 from January 2007.

This information highlights key points related to cell-free DNA (cfDNA) screening, which is the technology used in noninvasive prenatal testing (NIPT).

What is new in cfDNA screening?

Practice Bulletin #163 now recognises that cfDNA screening is an option for determining the risk of fetal aneuploidy in all pregnant women, regardless of maternal age, and highlights follow-up recommendations for patients with a positive result or a test failure.

Women whose cfDNA test results are not reported, are indeterminate, or are uninterpretable (eg, a no-call test result) should receive further genetic counselling, and the offer of comprehensive ultrasound evaluation and diagnostic testing because of an increased risk of aneuploidy.”

Key facts about cfDNA screening

  • cfDNA screening is not a substitute for diagnostic testing.
  • All patients with positive cfDNA test results should be offered confirmatory diagnostic testing before any irreversible decision, such as pregnancy termination, is made.
  • The positive predictive value (PPV) of cfDNA screening is dependent on the prevalence of the condition.

General recommendations

  • All women, irrespective of maternal screening and diagnostic testing.
    • Ideally, testing options should be discussed at the first prenatal visit.
    • The risk of fetal aneuploidy, and the benefits, and limitations of different testing options should be reviewed with the patient—aneuploidy testing should be an informed patient choice.
  • Its not cost effective to perform multiple screening tests in parallel
  • Patients who conceive after preimplantation genetic screening (PGS) for aneuploidy should be offered aneuploidy screening and diagnostic testing because of the potential for false-negative results with PGS.

Disclaimer: This summary is NOT intended to highlight the benefits and limitations of all screening and diagnostic options for pregnant women. This summary is also NOT intended to review all the recommendations and discussion included in Practice Bulletin #163, and is NOT intended to make recommendations relating to the practice of medicine or to substitute for the independent professional judgment of a licensed physician.

Technology of Choice

Data shows Illumina next-generation sequencing is the NIPT technology of choice.

of Choice

Data shows Illumina next-generation sequencing is the NIPT technology of choice

Published support of next generation sequencing (NGS)

Noninvasive prenatal testing (NIPT) provides accurate information about major chromosome abnormalities in a fetus as early as 10 weeks gestation using a single maternal blood draw.

  • Next-generation sequencing (NGS) is the most-published method for performing NIPT1,2
  • 99.7% of NIPT samples in published studies were run on Illumina NGS technology (Table 1)

A PubMed search for “cell-free, DNA, prenatal,” “noninvasive prenatal testing,” and “noninvasive prenatal screening” was performed on July 25, 2016. All validation and clinical studies using unique samples were included, where a current clinical NIPT provider performed sample analysis. Case studies, review articles, and studies published in a language other than English were excluded. A total of 76 published studies were surveyed. Data calculations on fi Illumina, Inc. 2016. NGS = next-generation sequencing; either whole-genome or targeted LDTs = laboratory developed tests.* In 2014, Ariosa switched from sequencing to arrays for clinical samples despite limited published data on this platform.


1. The American College of Obstetricians and Gynecologists. Committee Opinion:Cell free DNA screening for fetal aneuploidy. Committee-Opinions/Committee-on-Genetics/Cell-free-DNA-Screening-for-Fetal-Aneuploidy. Published June 26, 2015. Accessed August 5, 2015.
2. Benn P, Borell A, Chiu R, et al. Position statement from the Aneuploidy Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis.Prenat Diagn.

Accurate and Reliable Testing

Accurate and Reliable Testing

The Illumiscreen prenatal test uses proven NGS technology to provide accurate NIPT results with the lowest failure rate

What is test failure?

For noninvasive prenatal testing (NIPT), test failure indicates that no call for chromosomal status can be made. This is an important factor in the reliability and clinical utility of NIPT. NIPT test failure rates vary significantly based on the test. Using whole-genome NGS, the Illumiscreen prenatal test from Illumina achieves the lowest
test failure rate in NIPT (Figure 1).

The impact of test failure?

As test failure is really an inconclusive result, it leads to increased anxiety on the part of the patient and the physician, and it can potentially lead to an increased number of follow-up invasive procedures to obtain information. Although ordering a second blood draw to repeat NIPT is an option, there are no guarantees that repeated NIPT test will provide a definitive result. In fact, as many as 65% of patients who receive a no-call result on their first draw fail to receive a conclusive result, even after factoring in repeat attempts.

1,*An additional concern related to test failure rate is that methods that do not use whole-genome sequencing (WGS) have higher test failure rates. According to the Society for Maternal-Fetal Medicine (SMFM), “women with failed cfDNA tests are at an increased risk with aneuploidy, and therefore need careful counselling about further testing, including the offer of diagnostic testing.” 2 With a lower test failure rate, whole-genome NGS-based assays are more likely to detect these aneuploidies the first time.

Fig. 1 Test failures may lead to invasive procedures. – Theoretical example of the number of invasive procedures requested due to NIPT failure and false-positive rates of the assays. Failure rates include assay failures and samples rejected to a low fetal fraction. Assay failure rate for the Harmony test is based on NGS studies and may not be consistent with actual test results achieved using the array-based Harmoney Test currently in use. *This 65% includes test failures from redraws and patients that either chose not to submit a second sample or are ineligible for a redraw due to specific features that prevent resolution with SNP-based NIPT (ie, large regions exhibiting loss of heterozygosity [LOH]. Affected pregnancies with a screening test failure were excluded from the number of detected T21.

1.Dar P, Curnow KJ, Gross SJ, et al. Clinical experience and follow-up with large scale single-nucleotide polymorphism-based non-invasive prenatal aneuploidy testing. Am J Obstet Gynecol . 2014;211(5):527.e521-517.
1.Cell-Free DNA Screening – Publications. Society for Maternal-Fetal Medicine. Accessed June 5, 2015.
3a. Taneja PA, Snyder HL, de Feo E, et al. Noninvasive prenatal testing in the general obstetric population: clinical performance and counselling considerations in over 85,000 cases. Prenat Diagn. 2015;doi:10.1002/pd.4766.
3b. Mccullough RM, Almasri EA, Guan X, et al. Noninvasive prenatal chromosomal aneuploidy testing—clinical experience: 100,000 clinical samples. PLoS One. 2014;9:e109173. 3c. Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med . 2015;doi: 10.1056/NEJMoa1407349.
3d. Pergament E, Cuckle H, Zimmermann B, et al. Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstet Gynecol. 2014;124(2 Pt 1):210-218.
3e. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011;31(1):7-15. Wald NJ, Rodeck C, Hackshaw AK, et al. SURUSS in perspective. Semin Perinatol . 2005;29(4):225-235.