High diagnostic yield of family echocardiographic screening of children with bicuspid aortic valve

Aims Bicuspid aortic valve (BAV) is present in 0.8% of newborns, with associated aortopathy in 33%. While the prevalence of BAV and associated aortopathy in first-degree relatives of symptomatic BAV patients ranges from 5-10% and 5-32%, data from unselected probands are limited. Uniform family screening guidelines are lacking. We aimed to determine the prevalence of BAV and aortopathy in first-degree relatives of children diagnosed neonatally with BAV. Methods and results In this case-control family-study based on the Copenhagen Baby Heart Study (n>25,000 newborns enrolled 2016-2018), first-degree relatives of newborns with BAV (cases) or tricuspid aortic valve (controls) were examined with ech1ocardiography. BAV was classified using Sievers and Schmidtke’s system. Aortopathy was defined as aortic Z-score ≥2 in children or exceeding reference values in adults. Controls were matched on index-child sex, maternal age, parity, and singleton/twin status. In total, 380 relatives of 131 probands and 210 relatives of 76 controls were included. BAV was diagnosed in 36 relatives (9.5%) in the case group vs five (2.4%) in controls (p<0.05). Isolated aortopathy was seen in 29 (7.6%) vs seven (3.3%) relatives (p<0.05), and aortic regurgitation (mild) in 32 (8.4%) vs eight (3.8%) (p<0.05). The total yield of BAV and/or aortopathy was 65 (17.1%) in the case group (42% of families) vs 12 (5.7%) in controls (13% of families) (p<0.001). Conclusions First-degree relatives of children with BAV exhibited a three-fold higher prevalence of BAV and/or aortopathy compared to controls, and a twelve-fold higher risk of BAV than the general population, supporting family screening.