Abstract 13520: Impaired Prenatal Brain Development Predicts Adverse Neurodevelopmental Outcomes in Infants With Congenital Heart Disease

Introduction:Fetuses with complex congenital heart disease (CHD) are at high risk for impaired brain development. However, the relationship between altered fetal brain development and infant neurobehavioral outcomes in CHD remains largely unknown.Hypothesis:We hypothesized that impaired fetal brain volumetric growth and cortical folding in CHD would predict impaired infant neurodevelopment.Methods:We prospectively recruited women with pregnancies complicated by a fetal CHD diagnosis. Women underwent a fetal MRI on a GE 1.5T scanner. Volumes of fetal total brain, cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem were quantified. Cortical folding included local gyrification index, sulcal depth, and surface area. We completed Bayley Scales of Infant and Toddler Development III and Infant-Toddler Social and Emotional Assessment at 18 months. Generalized estimating equations were used to measure associations between fetal brain measures and infant neurodevelopment outcomes.Results:We enrolled 186 mother/baby dyads who underwent 250 MRIs between 20-39 gestational weeks. Seventy-seven had single-ventricle (SV) CHD and 109 had two-ventricle (2V) CHD. Forty-nine subjects died and 133 infants underwent neurodevelopment testing at a mean age of 19.6 months. Decreased fetal brain volumes and delayed cortical folding (all p<0.05) were associated with poorer infant cognitive outcomes. Impairments in fetal cerebellum (p=0.004), cortical (p=0.05) and deep gray matter (p=0.03) volumes, and cortical folding measures (all p<0.01) were associated with language delays. Reduced prenatal cortical gray matter volume (p=0.008), gyrification (p=0.02), and surface area (p=0.05) were associated with motor delays. Infants with SV CHD had lower competence scores compared to 2V CHD.Conclusions:We report that impairments in fetal brain growth and cortical folding predict adverse cognitive, language and motor outcomes in CHD. Infants with SV CHD showed greater susceptibility to social-emotional problems compared to those with 2V CHD. These data suggest that impaired prenatal regional brain growth disturbances and delayed cerebral cortical development are important biomarkers for later neurobehavioral dysfunction.