Increased Nuchal Translucency in Fetuses With a Crown-Rump Length of < 45 mm: Clinical Outcomes and Diagnostic Implications

TL;DR

This study shows that increased nuchal translucency in early pregnancies can predict chromosomal and structural abnormalities, even when below standard size thresholds.

Contribution

The study provides new evidence that NT measurements in fetuses under 45 mm CRL have significant diagnostic value.

Findings

32.2% of fetuses with CRL < 45 mm and increased NT had chromosomal abnormalities, mostly trisomy 18.

An NT cut-off of 3.89 mm predicted abnormal karyotype with 79.1% sensitivity and 55.3% specificity.

29.9% of chromosomal abnormalities would be missed by cell-free DNA screening alone in this group.

Abstract

Background/Objectives: Nuchal translucency (NT) measurement is an established first-trimester screening tool for chromosomal abnormalities. However, standardized risk assessment models are only validated for fetuses with a crown-rump length (CRL) between 45 and 84 mm. This study investigates the clinical significance of increased NT in fetuses with a CRL between 35 and 45 mm.

Methods: This retrospective study analyzed 208 singleton pregnancies with a CRL < 45 mm and an NT ≥ 2.5 mm, examined at two tertiary prenatal centers between 2008 and 2024. Data on chromosomal findings, structural anomalies, and pregnancy outcomes were collected through follow-up. Statistical analyses included univariate, bivariate, and receiver operating characteristic curve analysis to determine optimal NT cut-off values for predicting adverse outcomes.

Results: Chromosomal abnormalities were present in 67/208 cases (32.2%), with trisomy 18 being the most frequent. Malformations were detected in 46.7% of cases with available follow-up. The optimal NT cut-off for predicting an abnormal karyotype was 3.89 mm (sensitivity 79.1%, specificity 55.3%). Among fetuses with NT ≥ 5.5 mm, the rate of adverse outcomes reached 83.7%. Notably, 29.9% of chromosomal abnormalities would not have been detected by cell-free DNA screening for aneuploidy alone. Overall, the presence of increased NT, even below the standard CRL threshold, was associated with a significantly elevated risk of genetic and structural abnormalities as well as adverse pregnancy outcomes.

Conclusions: NT measurement in fetuses with CRL < 45 mm provides clinically relevant prognostic information. Elevated NT in this early gestational window is significantly associated with chromosomal anomalies, structural defects, and poor pregnancy outcomes. Reliance on cell-free DNA screening for aneuploidy alone in this cohort may miss a substantial proportion of abnormal cases. Early NT assessment should prompt comprehensive diagnostic evaluation and genetic counseling, even when the CRL is below 45 mm.

Figures