Prenatal cardiac biometries and flow assessments in fetuses at 20 weeks with a bicuspid aortic valve compared to healthy controls: a multicenter, cohort study.

Objectives To investigate the prenatal cardiovascular changes and biometries in fetuses with bicuspid aortic valve (BAV) diagnosed neonatally compared to heart-healthy controls. Methods In the Copenhagen Baby Heart Study, all neonates born in Copenhagen were offered echocardiography within the first 4 weeks of life from April 2016 to October 2018. The study included 25,556 children. The mothers were recruited at the 2nd -trimester anomaly scan performed at 18+0 to 22+6 weeks of gestation. From February 2017 (Rigshospitalet) and September 2017 (Herlev and Hvidovre Hospital) the documentation from the 2nd -trimester anomaly scan was supplemented with the four-chamber view with flow across the valves, the sagittal view of the aortic arch, the mid-umbilical artery flow (pulsatility index, PI), and the ductus venosus flow (PI). All images were evaluated by two investigators, and cardiac biometries were measured (55 cases with BAV and 8,316 controls). All cases with BAV neonatally were assessed by a specialist. We also analyzed maternal characteristics and 1st - and 2nd -trimester biomarkers. Results We identified 55 infants with BAV and 8316 heart-healthy controls in the period with extended prenatal cardiac image documentation. We found three times as many smoking mothers of children born with BAV as compared to heart-healthy controls (9.1 % vs. 2.7%, p=0.003). All the other baseline characteristics were similar. We found a significantly larger diameter of the aorta at the aortic valve in fetuses with BAV (3.1 mm vs. 3.0 mm (mean difference 0.12 mm (95% CI 0.03;0.21)), as well as a significantly larger diameter of the pulmonary artery at the pulmonary valve (4.1 mm vs. 3.9 mm (mean difference 0.15 mm (95% CI 0.03;0.28)). When converted to Z-scores and Bonferroni corrected, the results were no longer statistically different. Lastly, pregnancy associated plasma protein-A (PAPP-A) multiple of the median (MoM) was significantly lower in the BAV group (0.85 vs. 1.03, p=0.04). Conclusion Our results suggest that fetuses with BAV may have a larger aorta diameter at the location of the valve measured in the left ventricular outflow tract image as well as a larger pulmonary artery diameter at the location of the valve measured in the three-vessel view at 20 weeks' gestation. Moreover, we found an association between maternal smoking and low PAPP-A MoM and BAV in the fetus. This article is protected by copyright. All rights reserved.