Increased nuchal translucency thickness and normal chromosomal microarray: Danish nationwide cohort study.

Objective: To assess the outcome of pregnancies with increased fetal nuchal translucency (NT) thickness and a normal result from chromosomal microarray (CMA) vs conventional karyotyping.

Methods: This was a Danish nationwide registry-based cohort study of all singleton pregnancies seen for combined first-trimester screening between 2008 and 2018. Data on NT thickness and pregnancy outcome were retrieved from the Danish Fetal Medicine Database, whereas data on cytogenetic and molecular karyotypes were retrieved from the Danish Cytogenetic Central Register. Pregnancies were stratified according to NT thickness, and we computed the prevalence of chromosomal aberration, termination of pregnancy (due to non-genetic abnormal findings aside from increased NT), pregnancy loss, major congenital malformation and unaffected live birth (live birth ≥ 24 weeks' gestation with no chromosomal aberration or major congenital malformation diagnosed). The prevalence of the different outcomes was further estimated for pregnancies with increased NT (≥ 3.5 mm) and a normal CMA result. Finally, to assess the impact of CMA compared with conventional karyotyping for increased NT, we compared the prevalence of chromosomal aberrations and each pregnancy outcome between the periods 2008-2012 and 2014-2018 (during which < 3% and > 60%, respectively, of pregnancies with increased NT were examined using CMA).

Results: We identified 557 896 pregnancies with a NT measurement for which outcome data were registered. Fetal NT was ≥ 3.5 mm in 3717 (0.7%) pregnancies, of which 3368 (91%) underwent genetic examination. The prevalence of chromosomal aberrations increased significantly with increasing NT thickness, from 21% in pregnancies with NT of 3.5-4.4 mm to 69% in pregnancies with NT ≥ 6.5 mm. Trisomies 21, 18 and 13 accounted for the majority of chromosomal aberrations diagnosed in all subgroups of increased NT (range, 61-87%). In pregnancies with increased NT and a normal CMA result, the prevalence of unaffected live birth decreased significantly from 87% for NT of 3.5-4.4 mm to 29% for NT ≥ 6.5 mm. Increased uptake of CMA during 2014-2018 compared with 2008-2012 slightly increased the detection of submicroscopic aberrations. However, a normal CMA result, compared with a normal result from conventional karyotyping, did not substantially improve the prognosis in pregnancies with increased NT.

Conclusions: Our study reaffirms the association between increased NT and chromosomal aberrations. Although CMA improves diagnostic resolution in pregnancies with increased NT, a normal test result does not substantially impact the prevalence of unaffected live births. This highlights the ongoing need for accurate clinical guidance and continued research, especially as whole-genome sequencing is increasingly adopted in prenatal care. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.