How Useful is Nuchal Translucency in Detecting Chromosomal Abnormalities Missed by Genome-Wide NIPT and What Measurement Threshold Should Be Used?

May Phoo Han; Ana Elizabeth Gomes de Melo Tavares Ferreira; James Elhindi; Andrew C McLennan; Fergus Scott

doi:10.1002/pd.6742

How Useful is Nuchal Translucency in Detecting Chromosomal Abnormalities Missed by Genome-Wide NIPT and What Measurement Threshold Should Be Used?

Prenat Diagn. 2025 Jan 3. doi: 10.1002/pd.6742. Online ahead of print.

Authors

May Phoo Han¹, Ana Elizabeth Gomes de Melo Tavares Ferreira^{1

2}, James Elhindi³, Andrew C McLennan^{2

4}, Fergus Scott^{1

2}

Affiliations

¹ Discipline of Women's Health, University of New South Wales, Randwick, Australia.
² Sydney Ultrasound for Women, Sydney, Australia.
³ Women's & Newborn Health Department, Westmead Hospital, Westmead, Australia.
⁴ Discipline of Obstetrics, Gynaecology and Neonatology, University of Sydney, Sydney, Australia.

PMID: 39754320
DOI: 10.1002/pd.6742

Abstract

Introduction: Genome-wide non-invasive prenatal testing (gwNIPT) has screening limitations for detectable genetic conditions and cannot detect microdeletions/microduplications (MD) or triploidy. Nuchal translucency (NT) increases with gestation and with genetic or structural abnormalities. This study aims to determine the utility of NT measurement in detecting genetic abnormalities not identified by gwNIPT and the optimal NT threshold value.

Methods: A 4-year retrospective study of singleton pregnancies undergoing first-line gwNIPT aneuploidy screening where invasive prenatal testing by CVS/or amniocentesis was subsequently undertaken. Population proportions for static and multiple of the median (MoM) NT cut-offs were derived from all 11-14 weeks ultrasound examinations.

Results: Among 919 pregnancies with gwNIPT and invasive testing, 338 had a single genetic abnormality. There were 9 false negative GwNIPT results and a further 26 undetectable abnormalities (18 MD, 8 triploidy) in this cohort. Twelve had a dual chromosomal abnormality, four of which returned a low-risk gwNIPT. Thirty-three "missed cases" also had a 13-week scan, to which the various NT threshold values (3.0 mm, 1.6 MoM, 3.5 mm, and 1.9 MoM) were applied. In only 3 (9%) cases did the NT exceed 3.0 mm with similar detection rates (DR) for all higher cut-offs. Static and MoM-based NT cut-offs had similar positive predictive values (PPV).

Conclusion: Enlarged NT measurement is a poor predictor of genetic abnormalities not identified by gwNIPT. When applied, the fixed NT cut-off of 3.5 mm provides a low FPR with a similar DR to lower cut-off thresholds, resulting in a higher PPV.