Supplementary Material for: Low-set ears: a new marker of fetal chromosomal anomalies

Introduction: To assess the clinical utility of low-set ears (LSE) as a novel 2D-ultrasound marker for the prenatal detection of chromosomal anomalies.

Methods: A multicenter cohort study including 1,331 singleton pregnancies between 11+2 and 34+6 weeks of gestation was conducted in the two participating centers to determine the performance of LSE as an aneuploidy marker. LSE was defined as a dichotomous marker using an axial plane of the fetal head in 2D ultrasound. Intra- and interobserver variability were assessed to ensure marker reliability. Efficacy in predicting chromosomal anomalies was assessed using LSE alone or in combination with aneuploidy screening.

Results: The axial plane of the fetal head, defined by both lenses and the cerebellum, was adopted for LSE detection. Intra-observer concordance Kappa index for LSE measurement was 1.0, and 0.82 for interobserver reliability. Among the 1,308 studied fetuses with complete data, there were 1,243 healthy newborns, 22 (1.7%) chromosomal anomalies, five other genetic disorders (0.4%), 34 fetal structural anomalies (2.6%), and four stillbirths (0.3%). LSE was observed in 30 fetuses: in 19 (86%) of the 22 fetuses with chromosomal anomalies, in all cases (5/5, 100%) with other genetic anomalies, and in six (18%) of the 34 malformed fetuses without a genetic disorder. All fetuses with LSE had an adverse outcome.

Conclusions: Our study supports using LSE as a potential 2D-ultrasound marker for chromosomal anomaly detection. Studies with a larger sample size and in high-risk populations are warranted to prove its clinical utility before this marker can be included in prenatal screening protocols.