First-Trimester Assessment of the Extended Fetal Cardiovascular System Using the CASSEAL 3 × 3 Framework: Feasibility, Reproducibility and Diagnostic Performance

Background: The Extended Fetal Cardiovascular System (EFCS) encompasses the cardiac, infracardiac, and supracardiac vascular territories that contribute to fetal cardiovascular development and function. The CASSEAL 3 × 3 framework was developed to provide a structured anatomical assessment of the EFCS. This study aimed to evaluate its feasibility, reproducibility, and diagnostic performance during first-trimester screening. Methods: In this prospective single-center study, singleton pregnancies undergoing ultrasound examination between 11 + 0 and 13 + 6 weeks of gestation were assessed using the CASSEAL 3 × 3 framework. Feasibility, examination time, use of complementary techniques, interobserver reproducibility, and diagnostic performance were evaluated. Prenatal follow-up and postnatal findings served as the reference standard. Results: A total of 288 pregnancies were included in the final analysis. Complete visualization of all nine axial views was achieved in 86.5% of examinations. Mean examination time was 12.5 ± 3.3 min. Higher gestational age increased the likelihood of complete visualization, whereas higher maternal body mass index reduced feasibility. Interobserver agreement was high, with no significant systematic differences between operators. Six suspected EFCS abnormalities were identified during first-trimester examination. Diagnostic performance demonstrated high specificity (99.64%) and negative predictive value (98.58%), whereas sensitivity was moderate and should be interpreted cautiously due to the limited number of confirmed abnormalities. Conclusions: The CASSEAL 3 × 3 framework is a feasible and reproducible approach for structured first-trimester assessment of the EFCS. Diagnostic performance estimates should be interpreted cautiously given the limited number and spectrum of confirmed abnormalities and the use of a composite reference standard without systematic postnatal echocardiography. The framework may be better suited to specialized fetal medicine settings or as an adjunct to routine first-trimester assessment rather than as a universal screening tool.