Abstract 1159: Impaired Brain Metabolism in Fetuses with Congenital Heart Disease
Unmet metabolic demands of accelerated third trimester fetal brain development may underlie the high prevalence of neurologic dysfunction in the newborn with CHD. Magnetic resonance spectroscopy (1H-MRS) measures features of brain metabolism, including N-acetyl aspartate (NAA), a neuro-axonal marker and indicator of mitochondrial function, and lactic acid, a product of anaerobic metabolism. In this prospective study we performed 1H-MRS in normal fetuses and those with CHD to test the hypothesis that fetuses with CHD will demonstrate impaired brain metabolism in the third trimester compared to healthy controls.
Methods: We performed brain 1H-MRS studies to detect the presence of lactate and measure NAA/Choline (NAA/Cho) ratios in normal fetuses and those with CHD. Fetal echo was used to measure estimated aortic and pulmonary output, and umbilical and cerebral flow in all fetuses with CHD. Cerebral arterial oxygen and glucose levels were estimated as normal or abnormal based on type of CHD, intracardiac streaming/mixing, and expected delivery of umbilical venous blood to the brain.
Results: We studied 75 fetuses (median GA 30 wks, 25–37 wks), 39 healthy controls and 36 with CHD: HLHS (16), TGA (8), pulmonary atresia (3), and other (9). NAA/Cho increased progressively over the third trimester in normal fetuses, from ~0.2 at 26 wks to ~0.8 at 36 wks (r=0.98, p<0.001). In fetuses with CHD, however, the increase in NAA/Cho was much slower, and significantly and progressively lower with advancing GA (p<0.001). In multivariable analysis controlling for GA, absence of antegrade flow in the aortic arch (p<0.01), low estimated cerebral arterial oxygen-glucose levels (p<0.001), and presence of lactate (p<0.001) were independently associated with lower NAA/Cho. Lactate was identified in 7 (20%) fetuses with CHD (5 HLHS; 2 TGA) and no controls. Fetuses with lactate had the lowest GA-adjusted NAA/Cho.
Conclusions: These are the first in vivo fetal data to show impaired cerebral neuro-axonal development and metabolism in the fetus with CHD, likely due to a variable combination of substrate delivery (flow-oxygen-glucose). Our data support the hypothesis that mechanisms leading to increased neurodevelopmental disability in children with CHD may begin in fetal life.