The IONA® test recommended for twin pregnancies screening for Down’s syndrome – 7 April 2021

In recent years, fertility treatments and the fact women are having babies later has made multiple births more common. In 2016, around 12,000 sets of twins and about 190 sets of triplets or more were born in the UK. That means about 1 in every 65 births in the UK today are twins, triplets or more.1 Extensive studies have been carried out for cell-free DNA (cfDNA) testing in singleton pregnancies with sample numbers into the hundreds of thousands of women. In contrast, data in twin pregnancies are much scarcer, with only 11 studies previously published.2 Recently, Yourgene Health collaborated with 6 centres across the UK to conduct a prospective study, published in the American Journal of Obstetrics and Gynaecology , involving more than 1,000 women with twin pregnancies. The study has shown the Non-Invasive Prenatal Testing (NIPT), namely the IONA® test, to be effective and safe in detecting Down’s syndrome and therefore recommends that NIPT, such as the IONA® test, should be the primary test offered for Down’s syndrome (trisomy 21) screening in twins. 2 As a result, this study is of great significance as there is potential for NIPT to be useful in twin pregnancies, thereby reducing the need for invasive testing which carries the risk of losing one or more fetus. Non-invasive prenatal testing (NIPT) is a screening test used to detect the risk that a fetus will be born with certain genetic conditions. It can be performed as early as 10 weeks in pregnancy and only requires a blood sample from the mother. Other key significant conclusions, we were able to derive from the study include: The IONA® test shows a detection rate of >99.99% for Trisomy 21 The incidence of trisomy 21 is higher in twin than singleton pregnancies, furthermore first trimester combined screening (FTCT) in twin pregnancies has a lower detection rate (DR) (75%) and higher false positive rate (FPR) (7%) than singleton pregnancies3,4.  This study confirms that NIPT using cfDNA is the most accurate screening test for trisomy 21 in twin pregnancies (>99.99%), with screening performance similar to single pregnancies and a very low failure rates of just 0.31%. As expected, it was concluded that the predictive accuracy for trisomies 18 and 13 may be less due to biological factors. The IONA® test gives a valid result even with low fetal fraction  The mean fetal fraction in the study was 12.2% (range, 3%-36%); of which 9 samples with 3% fetal fraction also provided a valid result indicating that the IONA® test is valid for even low fetal fractions. Fetal fraction is the term given to the proportion of cfDNA belonging to the placenta found in the mother’s blood. Factors known to be associated with a lower fetal fraction in singleton pregnancies include in vitro fertilization (IVF) conception and higher maternal weight, two factors that are more common in twin than singleton pregnancies. The study was carried out at six fetal medicine  centres across the UK, with lead author, Professor Asma Khalil who is based at St George’s University Hospitals NHS Foundation Trust. St George’s University Hospitals NHS Foundation Trust is the largest healthcare provider, major teaching hospital and tertiary centre for south west London, Surrey and beyond – serving a population of 3.5 million. The other centres involved were: Leicester Royal Infirmary; the Central Manchester University Hospitals NHS Foundation Trust; Norfolk and Norwich University Hospitals NHS Foundation Trust; Leeds General Infirmary, and John Radcliffe Hospital in Oxford, United Kingdom. This follows on from a long-standing clinical relationship with these six key fetal medicine centres that were involved with the original IONA test clinical publication in 2015. 5 It is testament to the high quality and reliable performance of the IONA test that the majority of these fetal medicine centres are using it for their NIPT offering to their high-risk patients. Victoria Hutchinson, Clinical Lead at Yourgene states: “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. “ To read the full publication, please click here. The IONA® test is available as clinical service, with samples analysed at Yourgene Health’s state of the art genomics laboratory in Manchester, UK with results available in 2-5 days. In addition, the IONA® test is a complete CE-IVD product for labs wishing to offer their own in-house non-invasive prenatal testing (NIPT) service. Please email to find out more about either of these options. Participants in the study were recruited before the COVID-19 outbreak started, while the analysis of data and writing of the paper was carried out during the pandemic. References
  2. AJOG. 2021 January 15. Doi: 10.1016/j.ajog.2021.01.005. Noninvasive prenatal screening in twin pregnancies with cell-free DNA using the IONA® test: a prospective multicenter study. Khalil A, Archer R, Hutchinson V, Mousa H. A, Johnstone E. D, Cameron M. J, Cohen K.E, DPhil C.I, Kelly B, Reed K, Hulme R . & Papageorghiou A. T.
  3. Mutton D, Alberman E, Hook EB. Cytogenetic and epidemiological findings in Down syndrome,England and Wales 1989 to 1993. National Down syndrome Cytogenetic Register and theAssociation of Clinical Cytogeneticists. J MedGenet 1996;33:387–94.
  4. Spencer K, Nicolaides KH. Screening for trisomy 21 in twins using first trimester ultrasoundand maternal serum biochemistry in a one-stop clinic: a review of three years experience. BJOG 2003;110:276–80.
  5. Ultrasound Obstet Gynecol. 2015 Oct 23. DOI: 10.1002/uog.15791. Clinical evaluation of the IONA® test: a non-invasive prenatal screening test for Trisomy 21, 18 and 13. Papageorghiou A, Khalil A, Forman M, Hulme R, Mazey R, Mousa HA, Johnstone ED, McKelvey A, Cohen KE, Risley M, Denman W & Kelly B.