Enlarged NT (>= 3.5 mm) in the first trimester - not all chromosome aberrations can be detected by NIPT

Gosia Srebniak, Charlotte Wit, Karin Diderich, LCP Govaerts, Marieke Joosten, Maarten Knapen, Marnix Bos, Gerda Bruinsma, Mieke Koningen, Attie Go, Robert-Jan Galjaard, D Opstal

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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. Method: 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. Conclusion: 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.
Original languageUndefined/Unknown
JournalMolecular Cytogenetics
Publication statusPublished - 2016

Research programs

  • EMC MGC-02-52-01-A
  • EMC MGC-02-96-01
  • EMC MM-04-44-02

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