Why Offer Harmony? The ISPD and ACMG Call for NIPT cfDNA

Performance of the Harmony test

The Harmony test delivers consistent, industry-leading performance for trisomy 21, trisomy 18 and trisomy 13 across clinical studies.³

22q11.2 microdeletion 

22q11.2 microdeletion, an absence of a small piece of chromosome 22,⁴ happens in about 1 in 1000 pregnancies.^5,6 It is the second most common genetic cause of heart defects and developmental delay after Down syndrome,⁷ and is the underlying cause of DiGeorge and velocardiofacial syndromes (VCFS). 22q11.2 microdeletion is not reliably detected by routine prenatal screening or karyotype.⁷

Unlike trisomies, maternal age is not a risk factor for the microdeletion⁵ and family history cannot reliably predict its occurrence, as more than 90% of affected individuals have no family history.⁸

The performance of the Harmony test for 22q11.2 microdeletion has been evaluated in a study including over 1900 samples, including 129 with confirmed deletions. The Harmony test was able to reliably identify pregnancies at risk for 22q11.2 deletions of 3Mb and smaller with a low false positive rate.⁵

Download 22q11.2 study summary

Sex chromosome aneuploidies

Individuals typically have two X chromosomes or one X and one Y chromosome. Any variation from the typical number of X and Y chromosomes in the cells is called a sex chromosome aneuploidy (SCA). SCAs have a combined prevalence of about 1:500.⁹ Conditions associated with SCAs have widely variable clinical features that are often subtle but can include birth defects, infertility and learning differences. Most SCAs are not reliably detected by routine prenatal screening.

Twin pregnancies

Performance of the Harmony test has been published in peer-reviewed studies including over 1,300 twin pregnancies and has been used in over 16,000 twin pregnancies across the world.^{10,11,12,13,14,15,16}

Clinical scenarios included in published Harmony twin studies

• Monochorionic twins
• Dichorionic twins
• Twins conceived with in vitro fertilization (IVF)
• Twins conceived naturally
• Pregnancies where both twins have aneuploidy
• Pregnancies where only one twin has aneuploidy
• First trimester testing
• Second trimester testing

Professional societies such as The International Society for Prenatal Diagnosis (ISPD) and American College of Medical Genetics and Genomics (ACMG) support offering NIPT as a first-line screen.

“The following protocol options are currently considered appropriate: cfDNA screening as a primary test offered to all pregnant women.”¹⁷

“ACMG recommends informing all pregnant women that NIPS is the most sensitive screening option for trisomy 21, trisomy 18, and trisomy 13.”¹⁸