The Harmony® Test
Harmony® Prenatal Test
The Harmony® Test is a prenatal screening test for chromosomal disorders. It is characterized by excellent clinical validation and high reliability. This high reliability of the Harmony® Test has been confirmed in numerous clinical studies which have been published in peer-reviewed scientific journals. In a meta-analysis of over 23,000 pregnancies, the Harmony® Test for trisomy 21 achieved a detection rate of 99.3%. The specificity for trisomy 21 is 99.96% 1.
Advantages of the Harmony® Test
>99% detection rate for trisomy 21 in published studies.
Barely any other NIPT method has been investigated in trials as thoroughly as the Harmony® Test. Due to the targeted cfDNA analysis using microarray technology, the Harmony® Test achieves a very high level of sensitivity. In the study by Stokowski et al. The Harmony® Test for trisomy 21 has a detection rate of 99.3% in over 23,000 pregnancies2.
Only 0.04% for trisomy 21.
In one of the largest studies on non-invasive prenatal tests (NIPT), due to the high number of cases (23,155 pregnancies), exact data on the specificity and false-positive rate of the Harmony® Test could be determined. The specificity for trisomy 21 is 99.96% (trisomy 13 and 18: 99.98%). The false positive rate of the Harmony® Test for trisomy 21 is only 0.04% (trisomy 13 and 18: 0.02%)2.
A test result cannot be obtained only in a small percentage of cases45.The Harmony® Test is thereby characterised by a very high success rate.
The probability that a Harmony® Test can be performed successfully or not depends largely upon how much cell-free fetal DNA (cffDNA) there is in the mother’s blood. The proportion of cffDNA depends on both the week of pregnancy (the earlier this is, the less cffDNA is found) and the mother’s weight (the higher this is, the less cffDNA will be found).
Average turn-around time of the results is 3 business days – at no extra cost.
The unique design of the Harmony® Test permits an average processing period of only three working days from receipt of the samples until the delivery of the results. This has been made possible by the use of microarray technology, which replaces time-consuming sequencing. The time needed for this laboratory step can thus be reduced significantly. Microarray technology is also superior to sequencing in terms of accuracy in this application 6
The Harmony® Test analyses only chromosomes 22, 21, 18, 13, and the X and Y chromosomes, which permits a significant increase in the method’s efficiency 7. Instead of randomly sequencing parts of the entire genome, the Harmony® Test focuses on the chromosomes of interest; this allows a much more detailed analysis of these chromosomes with the Harmony® Test than with conventional NIPT methods, which are based on sequencing the complete cell-free DNA (“Massively Parallel Shotgun Sequencing”, MPSS).
The consequences are a greater accuracy and much less laboratory time, which is also reflected in the low costs of the test. Thereby – independent of the desired test option – all samples are analyzed with the method published in numerous studies.
The Harmony® Test permits the detection of numerical chromosomal disorders in the unborn child by taking a sample of the mother’s blood, eliminating the risk miscarriage inherent in invasive methods. The informative value of the Harmony® Test, particularly for trisomy 21, is thus many times higher than traditional first trimester screening.
The Harmony® Test does have limitations, as it cannot detect mosaics or structural chromosomal changes. It is also not possible to identify any physical or other disorders of the unborn child. A number of these illnesses can be detected with an accurate ultrasound scan, often from the 12th/13th week of pregnancy. A genetic test such as the Harmony® Test complements, but never replaces, a thorough ultrasound scan.
The following table compares the available prenatal test methods:
Heparin treatment affects the GC content of a blood sample. NIPT tests based on “random massively parallel sequencing” (rMPS) therefore have more failed tests and false results 8, 9, 10.
The Harmony® Test uses the DANSR (Digital Analysis of Selected Regions) method. Thanks to this unique analysis of specific regions of DNA, the Harmony® Test is independent of the GC distribution in a sample 11.
Test variants
Harmony® Test
for trisomies 21,18, and 13
Harmony® Test
for trisomies 21, 18, 13, and X/Y (XO, XXX, XXY, XYY, XXYY)
Harmony® Test
for trisomies 21,18, and 13
Harmony® Test
for trisomies 21, 18, 13, and X/Y (XO, XXX, XXY, XYY, XXYY)
Fetal sex determination optional
In addition to the costs for the Harmony® Test itself, your physician will provide services associated with the Harmony® Test (counseling, blood draw, examination). Please enquire at your physician beforehand about the costs of these services. Without any extra costs it takes on average 3 business days to process the Harmony® Test after the sample is received by the laboratory.
(Business days = Mo-Fr, public holidays excluded)
The Harmony® Test is currently still a privately paid service, thus we advise checking coverage policies with your health insurance plan prior to having the Harmony® Test performed. In some cases it is possible to have costs reimbursed by health insurance plans upon application; we provide forms and documentation in our downloads section to give you the best possible assistance.
- Stokowski R, Wang E, White K, Batey A, Jacobsson B, Brar H, Balanarasimha M, Hollemon D, Sparks A, Nicolaides K, Musci TJ.: Clinical performance of non-invasive prenatal testing (NIPT) using targeted cell-free DNA analysis in maternal plasma with microarrays or next generation sequencing (NGS) is consistent across multiple controlled clinical studies. Prenat Diagn. 2015 Sep 1 ↩
- Stokowski R, Wang E, White K, Batey A, Jacobsson B, Brar H, Balanarasimha M, Hollemon D, Sparks A, Nicolaides K, Musci TJ.: Clinical performance of non-invasive prenatal testing (NIPT) using targeted cell-free DNA analysis in maternal plasma with microarrays or next generation sequencing (NGS) is consistent across multiple controlled clinical studies. Prenat Diagn. 2015 Sep 1 ↩
- Stokowski R, Wang E, White K, Batey A, Jacobsson B, Brar H, Balanarasimha M, Hollemon D, Sparks A, Nicolaides K, Musci TJ.: Clinical performance of non-invasive prenatal testing (NIPT) using targeted cell-free DNA analysis in maternal plasma with microarrays or next generation sequencing (NGS) is consistent across multiple controlled clinical studies. Prenat Diagn. 2015 Sep 1 ↩
- Lüthgens K, Grati FR, Sinzel M, Häbig K, Kagan KO. Confirmation rate of cell free DNA screening for sex chromosomal abnormalities according to the method of confirmatory testing. Prenat Diagn. 2020 Aug 17. doi: 10.1002/pd.5814. Epub ahead of print. PMID: 32804406. ↩
- Kagan, K. O., Sroka, F., Sonek, J., Abele, H., Lüthgens, K., Schmid, M., Wagner, P., Brucker, S., Wallwiener, D. and Hoopmann, M. (), First trimester screening based on ultrasound and cfDNA vs. first-trimester combined screening – a randomized controlled study. Ultrasound Obstet Gynecol. Accepted Author Manuscript. doi:10.1002/uog.18905 ↩
- Juneau K, Bogard PE, Huang S, Mohseni M, Wang ET, Ryvkin P, Kingsley C, Struble CA, Oliphant A, Zahn JM: Microarray-based cell-free DNA analysis improves noninvasive prenatal testing. Fetal Diagn Ther. 2014;36(4):282-6. doi: 10.1159/000367626. Epub 2014 Sep 12. ↩
- Eiben B, Glaubitz R, Kagan KO: Nichtinvasive Pränataldiagnostik ETS und NGS-basierte Tests. Med Gen 2014, Epub ahead of print. DOI 10.1007/s11825-014-0021-3 ↩
- Sparks AB, Wang ET, Struble CA, Barrett W, Stokowski R, McBride C, Zahn J, Lee K, Shen N, Doshi J, Sun M, Garrison J, Sandler J, Hollemon D, Pattee P, Tomita-Mitchell A, Mitchell M, Stuelpnagel J, Song K, Oliphant A. Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy. Prenat Diagn. 2012 Jan;32(1):3-9. doi: 10.1002/pd.2922. ↩
- Chiu RW, Sun H, Akolekar R, Clouser C, Lee C, McKernan K, Zhou D, Nicolaides KH, Lo YM. Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21. Clin Chem. 2010 Mar;56(3):459-63. doi: 10.1373/clinchem.2009.136507. ↩
- Fan HC, Quake SR. Sensitivity of noninvasive prenatal detection of fetal aneuploidy from maternal plasma using shotgun sequencing is limited only by counting statistics. PLoS One. 2010 May 3;5(5):e10439. doi:10.1371/journal.pone.0010439. ↩
- Sparks AB, Struble CA, Wang ET, Song K, Oliphant A. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012 Apr;206(4):319.e1-9. doi: 10.1016/j.ajog.2012.01.030. ↩
