Comment on: “Low-Set Ears: A New Marker of Fetal Chromosomal Anomalies”

Second-trimester ultrasound uses structural and soft markers to identify fetuses at increased risk for chromosomal abnormalities. In the first trimester, trisomy 21 risk is typically evaluated using nuchal translucency and biochemical markers, though additional sonographic findings can refine this assessment. Facial features are often altered in chromosomal syndromes, and children with trisomy 21 commonly exhibit abnormal ear structure, including low-set ears (LSEs). Although fetal ear morphology has been explored as an early trisomy marker using 3D ultrasound and artificial intelligence models, its value as a 2D sonographic marker remains unclear. This study evaluated whether LSE identified during the first-trimester ultrasound can serve as a marker for chromosomal abnormalities. This prospective cohort study enrolled pregnant individuals undergoing routine ultrasound at 11 weeks 2 days to 34 weeks 6 days of gestation from 2 care centers in Catalonia between 2022 and 2024. Exclusion criteria included nonviable pregnancy at the time of ultrasound, lack of aneuploidy screening, multiple gestation, or incomplete perinatal follow-up. Gestational age was determined by crown-rump length in the first trimester or biparietal diameter when earlier dating was unavailable. LSE was defined as the upper ear tip lying below an imaginary line connecting the midpoints of the orbits. Because the orbits and ears cannot be visualized simultaneously with a 2D ultrasound, a method was developed to approximate their relative position using postmortem analyses and fetal MRI. Ultrasounds were performed by experienced sonologists, and intraobserver and interobserver agreement was assessed using the kappa concordance index. Aneuploidy screening results, genetic diagnostic testing, and perinatal outcomes were recorded, and the diagnostic performance of LSE was evaluated alone and in combination with routine screening. LSE was assessed using a newly defined axial fetal head plane with the orbits anteriorly and the cerebellum posteriorly. LSE was diagnosed when the superior ear tips were not visualized in this plane. Intraobserver agreement was excellent (κ = 1.0), and interobserver agreement was high (κ = 0.82). Among 1308 fetuses with complete follow-up, 22 had chromosomal abnormalities, most commonly trisomy 21 and trisomy 18. LSE was identified in 30 fetuses and confirmed postnatally in nearly all evaluated cases. Of these, 19 had chromosomal abnormalities, 5 had other genetic disorders, and 6 had structural anomalies without an identified genetic cause. No healthy newborns had confirmed LSE. As a marker for chromosomal anomalies, LSE demonstrated 86% sensitivity, 100% specificity, a positive predictive value of 100%, and a negative predictive value of 99.8%. When combined with routine aneuploidy screening, LSE improved specificity from 89% to 100% while maintaining a high negative predictive value. The findings suggest that LSEs identified on 2D ultrasound may serve as a marker for chromosomal abnormalities and other genetic disorders. Unlike prior studies relying on 3D ultrasound or artificial intelligence–based analysis of fetal ear morphology, this approach can be incorporated into routine prenatal ultrasound with minimal added time. When combined with standard aneuploidy screening, LSE improved specificity while maintaining a high negative predictive value. Strengths include the prospective design, high interobserver reliability, and strong correlation with postnatal or postmortem findings. Limitations include the small number of chromosomally abnormal fetuses and the need for validation in larger and higher-risk populations. (Summarized from Baldrich-Martin E, Jalencas G, Mazano I, et al. Low-set ears: a new marker of fetal chromosomal anomalies. Fetal Diagn Ther. 2025 Nov 11:1-9. doi:10.1159/000548946).