# 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.

## Key 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.