Clinical evaluation of the IONA test: a non-invasive prenatal screening test for trisomies 21, 18 and 13.
OBJECTIVE
To evaluate the clinical accuracy of the IONA® test for aneuploidy screening.


METHODS
This was a multicenter blinded study in which plasma samples from pregnant women at increased risk of trisomy 21 underwent cell-free DNA analysis utilizing the IONA test. For each sample, the IONA software generated a likelihood ratio and a maternal age-adjusted probability risk score for trisomies 21, 18 and 13. All results from the IONA test were compared against accepted diagnostic karyotyping.


RESULTS
A total of 442 maternal samples were obtained, of which 437 had test results available for analysis and assessment of clinical accuracy. The IONA test had a detection rate of 100% for trisomies 21 (n = 43; 95% CI, 87.98-100%), 18 (n = 10; 95% CI, 58.72-100%) and 13 (n = 5; 95% CI, 35.88-100%) with cut-offs applied to likelihood ratio (cut-off > 1 considered high risk for trisomy) and probability risk score incorporating adjustment for maternal age (cut-off ≥ 1/150 considered high risk for trisomy). The false-positive rate (FPR) was 0% for trisomies 18 and 13 with both analysis outputs. For trisomy 21, a FPR of 0.3% was observed for the likelihood ratio, but became 0% with adjustment for maternal age.


CONCLUSIONS
This study indicates that the IONA test is suitable for trisomy screening in a high-risk screening population. The result-interpretation feature of the IONA software should facilitate wider implementation, particularly in local laboratories, and should be a useful addition to the current screening methods for trisomies 21, 18 and 13.
Fetal Medicine Unit, St George's University Foundation Hospitals NHS Trust, London, UK.|Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford, UK.
A T
AT
Papageorghiou
Fetal Medicine Unit, St George's University Foundation Hospitals NHS Trust, London, UK.
A
A
Khalil
Premaitha Health plc, Manchester, UK.
M
M
Forman
Premaitha Health plc, Manchester, UK.
R
R
Hulme
Premaitha Health plc, Manchester, UK.
R
R
Mazey
Department of Fetal and Maternal Medicine, Leicester Royal Infirmary, Leicester, UK.
H A
HA
Mousa
Tommy's Research Centre, Central Manchester Foundation Trust, Manchester, UK.
E D
ED
Johnstone
Fetal Medicine Unit, Norfolk and Norwich University Hospitals Foundation Trust, Norwich, UK.
A
A
McKelvey
Department of Fetal Medicine, Leeds General Infirmary, Leeds, UK.
K E
KE
Cohen
Premaitha Health plc, Manchester, UK.
M
M
Risley
Premaitha Health plc, Manchester, UK.
W
W
Denman
Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford, UK.
B
B
Kelly
D000293:Adolescent; D000328:Adult; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004314:Down Syndrome / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D005865:Gestational Age; D006801:Humans; D007621:Karyotyping; D008423:Maternal Age; D062145:Maternal Serum Screening Tests / Q000379:methods*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D018566:Pregnancy, High-Risk / Q000097:blood / Q000235:genetics; D016037:Single-Blind Method; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome; D055815:Young Adult
aneuploidy; diagnosis; fetal DNA; non-invasive; pregnancy; screening; sequencing; trisomy