The potential impact of NIPT as a second-tier screen on the outcomes of high-risk pregnancies with rare chromosomal abnormalities.
OBJECTIVE
To describe the potential impact of using noninvasive prenatal testing (NIPT) as a second-tier test, on the diagnosis and outcomes of pregnancies identified as high risk through first trimester screening (FTS) in a cohort of real pregnancies.


METHODS
Western Australian FTS and diagnostic data (2007-2009) were linked to pregnancy outcomes. Karyotype results from invasive prenatal testing in high-risk women were analysed. The outcomes of abnormal results that would not be detected by NIPT, assuming a panel of trisomy 21/18/13 and sex chromosome aneuploidies, and the likelihood of diagnosis in a screening model using NIPT as a second-tier test are described.


RESULTS
Abnormal karyotype results were reported in 224 of 1488 (15%) women with high-risk pregnancies having invasive diagnostic testing. NIPT potentially would have identified 85%. The 33 abnormalities unidentifiable by NIPT were triploidies (n = 7, 21%), balanced (n = 8, 24%) and unbalanced rearrangements (n = 10, 30%) and level III mosaicisms (n = 8, 24%). For conditions not identifiable by NIPT, fetal sonographic appearance was likely to have led to invasive testing for 10 of 17 (59%) pathogenic abnormalities. If a policy was adopted recommending invasive testing for FTS risk >1:50 and/or ultrasound detected abnormality, the residual risk of an unidentified pathogenic chromosomal abnormality in those without a diagnosis would have been 0.33% (95% CI 0.01-0.65%).


CONCLUSIONS
A screening model with NIPT as a second-tier for high-risk pregnancies would be unlikely to have changed the outcome for the majority of pregnancies. Optimising the diagnosis of rare pathogenic abnormalities requires clear indicators for invasive testing over NIPT.
Health Policy and Management, School of Public Health, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.
Susannah
S
Maxwell
Ultrasound Department, King Edward Memorial Hospital, Perth, Western Australia, Australia.|School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
Jan E
http://orcid.org/0000-0003-3928-3290
JE
Dickinson
PathWest Laboratory Medicine, QEII Medical Centre, Perth, Western Australia, Australia.|School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
Ashleigh
A
Murch
Health Policy and Management, School of Public Health, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.|School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.|PathWest Laboratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.
Peter
P
O'Leary
D000328:Adult; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002882:Chromosomes, Human, Pair 13; D016208:Databases, Factual; D004314:Down Syndrome; D005260:Female; D006801:Humans; D015994:Incidence; D007621:Karyotyping; D008423:Maternal Age; D048208:Nuchal Translucency Measurement / Q000379:methods*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D018566:Pregnancy, High-Risk; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies; D018570:Risk Assessment; D014314:Trisomy; D000073839:Trisomy 13 Syndrome; D014904:Western Australia
abnormal karyotype; prenatal diagnosis; prenatal screening; ultrasonography