Nuchal translucency of 3.0‐3.4 mm an indication for NIPT or microarray? Cohort analysis and literature review

Abstract

Introduction Currently fetal nuchal translucency (NT) ≥3.5mm is an indication for invasive testing often followed by chromosomal microarray. The aim of this study was to assess the risks for chromosomal aberrations in fetuses with a NT 3.0‐3.4 mm, to determine whether invasive prenatal testing would be relevant in these cases and to assess the residual risks in fetuses with normal non‐invasive prenatal test (NIPT) results. Material and methods A retrospective study and meta‐analysis of literature cases with NT between 3.0‐3.4 mm and two cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed: Rotterdam region (with a risk >1:200 and NT between 3.0‐3.4 mm) tested in the period July 2012‐ June 2019 and Central Denmark region (with a risk >1:300 and NT between 3.0‐3.4 mm) tested between September 2015 – December 2018. Results 522 fetuses were referred for invasive testing and chromosomal microarray. Meta‐analysis indicated that in 1:7.4 (13.5% (95% CI, 8.2‐21.5%)) fetuses a chromosomal aberration was diagnosed. 47/68 (69%) of these aberrant cases involved trisomy 21, 18 and 13 and would potentially be detected by all NIPT approaches. The residual risk for missing a (sub)microscopic chromosome aberration depends on the NIPT approach and it is the highest if NIPT was performed only for common trisomies ‐ 1:21 (4.8% (95% CI, 3.2‐7.3)). However, it may be substantially lowered if a genome‐wide 10Mb resolution NIPT test was offered (~1:464). Conclusions Based on these data we suggest that the NT cut‐off for invasive testing could be 3.0 mm (instead of 3.5 mm) due to the high risk of 1:7.4 for a chromosomal aberration. If women were offered NIPT first, there would be a significant diagnostic delay since all abnormal NIPT results need to be confirmed by diagnostic testing. If the woman had already received a normal NIPT result, the residual risk of 1:21‐1:464 for chromosome aberrations other than common trisomies, dependent on the NIPT approach, should be counseled. If a pregnant woman declines invasive testing, but still wants a test with a broader coverage of clinical significant conditions the genome‐wide >10Mb resolution NIPT test that detects most aberrations, could be proposed.