Can cell-free fetal DNA screening be utilized for the assessment of chromosomal abnormalities in fetuses with mildly increased nuchal translucency?

OBJECTIVES

This article investigates the theoretical detection rate of non-invasive prenatal screening (NIPS) and the residual risk of copy-number variations (CNVs) after normal NIPS results, for fetuses with isolated mild increased nuchal translucency (ImiNT), compared to chromosomal microarray analysis (CMA).

METHODS

A retrospective analysis was conducted on CMA results in a cohort with ImiNT (2.5 mm or 95th percentile ≤ NT < 3.5 mm). Theoretical detection rates and residual risk values were calculated for four NIPS panels-Basic NIPS-3, Basic NIPS-5, Expanded NIPS (ExpNIPS), and Genome-Wide (GW) NIPS-for common chromosomal aneuploidies and clinically significant CNVs.

RESULTS

In a cohort of 936 fetuses with ImiNT, 44 cases had clinically significant CMA results. Basic NIPS-3 could detect 10 cases (9 trisomy 21 and 1 trisomy 18), leaving a residual risk of 3.63% (1/28). Basic NIPS-5 detected 17 cases, including 7 sex chromosome abnormalities, reducing the residual risk to 2.88% (1/35). ExpNIPS identified 18 cases, adding one microdeletion compared to Basic NIPS-5, with a residual risk of 2.78% (1/36). GW NIPS detected 22 cases, finding 5 additional CNVs > 10 Mb compared to Basic NIPS-5, lowering the residual risk to 2.35% (1/43).

CONCLUSION

Using NIPS as a substitute for invasive prenatal diagnosis in cases of ImiNT should still be approached with caution. Couples must be ensured to understand the advantages and limitations of both methods. They should also be informed about the residual risk, ranging from 2.35 (1/43) to 3.63% (1/28), even after normal NIPS results. This understanding will help couples make informed decisions.