Ascending Aorta Size at Birth Predicts White Matter Microstructure in Adolescents Who Underwent Fontan Palliation

Abstract

Background In neonates with single ventricle, smaller ascending aorta diameter is associated with cerebral white matter ( WM ) microstructural abnormalities. We sought to determine whether this association persists into adolescence. Methods and Results Ascending aorta Z scores were obtained from first postnatal echocardiogram. Brain magnetic resonance imaging with diffusion tensor imaging was acquired in adolescence and used to obtain fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity in 33 WM tract regions of interest. Partial Pearson correlation coefficients were evaluated for associations between ascending aorta Z scores and WM microstructure measures, adjusting for sex, age at magnetic resonance imaging, scanner field strength, and Norwood status. Among 42 single ventricle patients aged 10 to 19 years, 31 had undergone the Norwood procedure as neonates. Lower ascending aorta Z scores were associated with lower fractional anisotropy in bilateral pontine crossing tracts ( P =0.02), inferior fronto‐occipital fasciculus ( P =0.02), and inferior longitudinal fasciculus ( P =0.01); left cingulum–cingulate bundle ( P =0.01), superior longitudinal fasciculus ( P =0.04), and superior longitudinal fasciculus–temporal component ( P =0.01); and right cingulum–hippocampal bundle (P =0.009) and inferior cerebellar peduncle ( P =0.01). Lower ascending aorta Z scores were associated with higher radial diffusivity and mean diffusivity in a similar regional pattern but not with axial diffusivity. Conclusions In adolescents with single ventricle, smaller aorta diameter at birth is associated with abnormalities of WM microstructure in a subset of WM tracts, mostly those located in deeper brain regions. Our findings suggest that despite multiple intervening medical or surgical procedures, prenatal cerebral blood flow may have a lasting influence on WM microstructure in single‐ventricle patients.

Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease

“…The volumetric reductions in our dataset may reflect disruption to this highly orchestrated pattern and contribute to abnormal connectivity and cortical development detected in children/adolescents with CHD. 10,11,[34][35][36][37] Animal models and data from preterm neonates suggest that components of subplate, intermediate, and ventricular zones are vulnerable to hypoxia-ischemia. Hypoxia-ischemia alters the maturational trajectory and synaptogenesis of subplate neurons.…”

“…10 Remarkably, this association persists into adolescence. 11 Other factors operating in utero may also influence longterm brain structure, including deleterious gene variants, 12 placental dysfunction, 13 socioeconomic status, 14,15 and environmental exposures (eg, alcohol 16 ).…”

Altered frontal white matter microstructure is associated with working memory impairments in adolescents with congenital heart disease: A diffusion tensor imaging study

“…There is evidence that microstructural changes are already evident at early life and may persist over time: white matter microstructure have been demonstrated in neonates with CHD (Hagmann et al., 2016; Karmacharya et al., 2018; Mulkey, 2014) and were associated with reduced functional connectivity in EEG (Birca et al., 2016). Zaidi and colleagues (Zaidi et al., 2018) demonstrated that the size of the aorta in neonates with a single ventricle heart defect predicted the anisotropy of the white matter microstructure in adolescents, suggesting a lasting influence of cerebral blood flow on white matter maturation.…”

Altered Cerebral Microstructure in Adults With Atrial Septal Defect and Ventricular Septal Defect Repaired in Childhood

“…Specifically, alterations in WM microstructure and network topology have been found associated with neurodevelopmental disabilities and clinical risk factors. 10 , 11 , 12 , 13 , 14 , 15 Despite the importance of gray matter (GM) integrity in relation to neurocognitive abilities and motor skills, studies on the long‐term impact of CHD on microstructural GM development are lacking, probably due to methodological restrictions.…”