Natural History and Evolution of Conotruncal Anomalies Diagnosed Before 16 Weeks' Gestation: A Multicenter Retrospective Cohort Study

Objective: To assess the natural history and evolution of conotruncal anomalies (CTAs) diagnosed before 16 weeks’ gestation, focusing on lesion progression, genetic associations, and pregnancy outcomes. A secondary aim was to establish nomograms for the fetal pulmonary artery and aorta between 12+0 and 15+6 weeks’ gestation in normal fetuses. Methods: This retrospective cohort study was conducted at two Italian tertiary fetal medicine centers between 2017 and 2023. Fetuses diagnosed with CTA on early fetal echocardiography (<16 weeks) were identified from institutional databases. Included anomalies were anterior malalignment ventricular septal defect (am-VSD), tetralogy of Fallot (TOF), TOF with pulmonary atresia (TOF- PA), truncus arteriosus (TA), double outlet right ventricle (DORV), transposition of the great arteries (TGA), congenitally corrected TGA (cTGA), and interrupted aortic arch type B (IAA-B). Only cases with postnatal or postmortem confirmation were included. Progression was defined as morphologic change requiring revision of diagnosis. Invasive genetic testing (CMA ± WES) was offered to all patients. Reference measurements of the great arteries were prospectively collected in normal fetuses between 12+0 and 15+6 weeks. Results: A total of 131 fetuses were diagnosed with CTA before 16 weeks; 101 fulfilled inclusion criteria. Sixty-one pregnancies (46.6%) were terminated, most commonly for abnormal genetic findings (mostly 22q11.2 microdeletion). Among 70 ongoing pregnancies, intrauterine demise occurred in 5 cases (7.1%) and postnatal death in 2 (2.9%). Lesion progression occurred in 19/70 (27.1%), mainly between the second and third trimesters. The most frequent evolutions were am- VSD to TOF (n=8) and TOF to TOF-PA (n=4). Nomograms for early aortic and pulmonary valve dimensions were established. Progressive TOF cases had pulmonary artery diameters below the 5th centile, while stable cases were above this range. Conclusions: CTAs diagnosed before 16 weeks are dynamic conditions, with one in four showing antenatal progression. Early diagnosis warrants detailed genetic assessment, serial echocardiography, and specialized prenatal counselling. Early vessel measurements may help identify fetuses at risk of evolution and guide tailored surveillance.