Outcome of fetuses with early increased nuchal translucency: systematic review and meta-analysis.

Objective: Nuchal translucency (NT) has been the mainstay of the first-trimester screening assessment for fetal aneuploidies. Although NT is typically measured between 11 and 14 weeks' gestation when fetal crown-rump length (CRL) is between 45 and 85 mm, recent studies suggest that fetuses with increased NT measured in the early first trimester of pregnancy are also at high risk of aneuploidy, genetic disorders or adverse pregnancy outcomes. The aim of this systematic review was to report the outcomes of fetuses with early increased NT before 11 weeks' gestation.

Methods: MEDLINE, EMBASE and Cochrane databases were searched from inception to August 2024. The inclusion criteria were studies reporting the outcome of fetuses with increased NT, defined according to an absolute cut-off or percentile in the original publication, and a CRL < 45 mm. The primary outcome was a composite score of adverse pregnancy outcome, including the presence of either chromosomal, genetic or structural anomalies, or perinatal loss. The secondary outcomes explored were: resolution of increased NT at the 11-14-week scan; chromosomal anomaly; copy-number variant detected on chromosomal microarray; single-gene disorder detected on next-generation sequencing; structural anomaly; perinatal loss, defined as the occurrence of miscarriage or fetal loss; and termination of pregnancy. All outcomes were explored in the overall population of fetuses with early increased NT, according to the resolution or persistence of increased NT and according to different NT thickness (2.5-3.4 mm, 3.5-4.4 mm and ≥ 4.5 mm). Random effects meta-analysis of proportions was used to combine the data and results were reported as pooled proportions with 95% CI.

Results: Five studies (401 fetuses with CRL < 45 mm presenting with increased NT) were included in the systematic review and three of these (269 fetuses) were included in the meta-analysis. Composite adverse pregnancy outcome complicated 42.0% (95% CI, 18.5-67.6%) of pregnancies presenting with early increased NT. Chromosomal or genetic anomaly at either pre- or postnatal assessment was reported in 40.2% (95% CI, 12.8-71.5%) of cases. Structural anomaly was identified on ultrasound in 5.9% (95% CI, 3.4-9.1%) of fetuses with early increased NT, and perinatal loss occurred in 9.7% (95% CI, 6.4-13.5%) of cases. Of the fetuses presenting with increased NT in the early first trimester of pregnancy, 48.8% (95% CI, 30.6-67.1%) showed resolution of the increased NT at the 11-14-week scan, and the increased NT persisted in 51.2% (95% CI, 32.9-69.4%). Composite adverse pregnancy outcome occurred in 64.2% (95% CI, 51.8-75.6%) of fetuses in which increased NT was persistent at the 11-14-week scan and in 19.4% (95% CI, 8.8-33.0%) of those in which the increased NT resolved. Finally, when considering different cut-offs of NT thickness, adverse pregnancy outcome occurred in 31.9% (95% CI, 14.4-52.6%) of fetuses with NT between 2.5 and 3.4 mm, 50.4% (95% CI, 30.1-70.7%) of those with NT between 3.5 and 4.4 mm and 70.2% (95% CI, 32.0-94.9%) of those with NT ≥ 4.5 mm.

Conclusion: Increased NT measured in the early first trimester of pregnancy is associated with an increased risk of adverse pregnancy outcome, chromosomal, genetic and structural anomalies, and perinatal loss, even in case of its resolution at the time of the 11-14-week scan. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.