Enlarged NT (≥3.5 mm) in the first trimester - not all chromosome aberrations can be detected by NIPT.
BACKGROUND
Since non-invasive prenatal testing (NIPT) in maternal blood became available, we evaluated which chromosome aberrations found in our cohort of fetuses with an enlarged NT in the first trimester of pregnancy (tested with SNP microarray) could be detected by NIPT as well.


METHODS
362 fetuses were referred for cytogenetic testing due to an enlarged NT (≥3.5 mm). Chromosome aberrations were investigated using QF-PCR, karyotyping and whole genome SNP array.


RESULTS
After invasive testing a chromosomal abnormality was detected in 137/362 (38 %) fetuses. 100/362 (28 %) cases concerned trisomy 21, 18 or 13, 25/362 (7 %) an aneuploidy of sex chromosomes and 3/362 (0.8 %) triploidy. In 6/362 (1.6 %) a pathogenic structural unbalanced chromosome aberration was seen and in 3/362 (0.8 %) a susceptibility locus for neurodevelopmental disorders was found. We estimated that in 2-10 % of fetuses with enlarged NT a chromosome aberration would be missed by current NIPT approaches.


CONCLUSIONS
Based on our cohort of fetuses with enlarged NT we may conclude that NIPT, depending on the approach, will miss chromosome aberrations in a significant percentage of pregnancies. Moreover all abnormal NIPT results require confirmatory studies with invasive testing, which will delay definitive diagnosis in ca. 30 % of patients. These figures are important for pretest counseling enabling pregnant women to make informed choices on the prenatal test. Larger cohorts of fetuses with an enlarged NT should be investigated to assess the additional diagnostic value of high resolution array testing for this indication.
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Malgorzata I
MI
Srebniak
Department of Obstetrics and Gynecology, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Merel C
MC
de Wit
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Karin E M
KE
Diderich
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Lutgarde C P
LC
Govaerts
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Marieke
M
Joosten
Department of Obstetrics and Gynecology, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands ; Foundation Prenatal Screening Southwest region of The Netherlands, Wytemaweg 80, Na-1509, 3015 CN Rotterdam, The Netherlands.
Maarten F C M
MF
Knapen
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Marnix J
MJ
Bos
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Gerda A G
GA
Looye-Bruinsma
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Mieke
M
Koningen
Department of Obstetrics and Gynecology, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Attie T J I
AT
Go
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Robert Jan H
RJ
Galjaard
Department of Clinical Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Diane
D
Van Opstal
Array; Microdeletion; NIPT; NT; Nuchal translucency; Prenatal diagnosis; Submicroscopic chromosomal abnormalities