Fetuses with nuchal translucency measurements as low as 2.0 mm have a higher probability of chromosomal abnormalities, suggests a recent study published in JAMA Network Open.¹ Fetuses with nuchal translucency measurements of 3.0 to less than 3.5 mm were 20 times more at risk of having abnormalities vs those with measurements <2.0 mm. The risk was 6-folds higher in fetuses with measurements of 2.5-3 mm and more than doubled when the nuchal transparency measurement ranged between 2 and 2.5 mm.

Kara Bellai-Dussault from the School of Epidemiology and Public Health, University of Ottawa, Canada and coauthors conducted this retrospective cohort study to explore how different nuchal translucency measurements correlate with the likelihood of specific cytogenetic outcomes in singleton pregnancies. For this they used data of all singleton pregnancies with an estimated delivery dates between September 2016 and March 2021 from the Better Outcomes Registry & Network, which serves as the perinatal registry for Ontario, Canada. The reference group for comparison consisted of pregnancies with a nuchal translucency measurement less than 2.0 mm. Chromosomal anomalies such as Down syndrome, Edwards syndrome, and Patau syndrome were identified through prenatal and postnatal cytogenetic tests conducted in Ontario laboratories. The results of cfDNA screening and clinical assessment at birth were added to the data from cytogenetic testing to identify pregnancies free of chromosomal abnormalities.

Analysis of data revealed that a nuchal translucency of less than 2.0 mm was present in the majority of the study group (86.9%; n=359 807) out of the 414,268 pregnancies that were included in the study. The mean maternal age at the predicted delivery date was 31.5 years. Chromosomal abnormalities were present in 0.5% of this group.

As the nuchal translucency measurement increased, the risk of chromosomal abnormalities increased. For pregnancies with nuchal translucency measurements of 3.0 to less than 3.5 mm, the adjusted risk ratio (ARR) was 20.33 and the adjusted risk difference (ARD) was 9.94%. When limited to chromosomal abnormalities outside the widely screened aneuploidies (excluding trisomies 21, 18, and 13 and sex chromosome aneuploidies), the ARR was 4.97 and the ARD was 1.40%.

The findings from this cohort study suggest a clear association between higher nuchal translucency measurements and the elevated risk of chromosomal anomalies. Those with nuchal translucency measurements less than 2.0 mm were at the least risk. The study further indicates that even after excluding the commonly screened chromosomal anomalies, there remains a significantly increased risk of anomalies not frequently checked for by many prenatal genetic screening programs associated with higher nuchal translucency measurements. Overall, this study underscores the importance of nuchal translucency measurements as a valuable screening tool in prenatal care. Even slight increases in nuchal translucency can potentially signal an elevated risk of chromosomal abnormalities.

A cut-off of 3.0 mm or greater or above the 99th percentile for the crown–rump length in the first trimester has been proposed by the American College of Obstetricians and Gynecologists (ACOG) for further diagnostic testing such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing.² This study, by suggesting that pregnancies with nuchal translucency measurements lower than the 3.0 mm threshold were associated with risk of chromosomal anomalies, may have practice changing implications for prenatal genetic screening.

References

1.   Kara Bellai-Dussault, et al. Ultrasonographic fetal nuchal translucency measurements and cytogenetic outcomes. JAMA Netw Open. 2024 Mar 4;7(3):e243689. doi: 10.1001/jamanetworkopen.2024.3689.

2.   American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol. 2020 Oct;136(4):e48-e69. doi: 10.1097/AOG.0000000000004084.