Objectives:
Term congenital heart disease (CHD) neonates demonstrate pre-operative (op) abnormal brain metabolism (reduced N-acetylaspartate (NAA), elevated lactate) on long echo MR spectroscopy (MRS). We sought to delineate associations between serial brain metabolism and patient and perioperative clinical factors in term neonates with CHD using short echo MRS. We measured NAA and lactate as well as other metabolites important for brain connectivity such as neurotransmitters glutamate/glutamine and GABA.
Methods:
Subjects were prospectively enrolled to undergo pre and post-op 3T short echo single voxel MRS of parietal white matter with absolute quantitation of 15 metabolites using LCModel. Neurodevelopment (ND) was assessed via 18 month Battelle Developmental Inventory. Linear and logistic regression with false discovery rate correction was used for statistical analysis.
Results:
Eighty subjects were enrolled 2009-2015 and 21 term CHD infants underwent both pre and post-op MRS. Eight infants had at least one MRS and ND. NAA and glutamate were significantly decreased post-op compared to pre-op (p<0.0001), with no significant difference in other metabolites. Pre-op factors including lower Apgar score, birth weight, head circumference and PaO2 and higher arterial pH and serum lactate were associated with lower NAA (p<0.002). Single ventricle anatomy was associated with low NAA, high myo-inositol and low glutamine/glutamate compared to two ventricles (p<0.01). Longer cardipulmonary bypass time, but not deep hypothermic circulatory arrest, was associated with reduced NAA (p<0.001). Post-op, global alteration in multiple serial brain metabolites (NAA, lactate, glutamate/glutamine, GABA, myo-inostol) were associated with longer ICU and hospital stay (p<0.03). In those with ND testing, high GABA correlated with low cognitive domain score, while high glutamine correlated with low motor score (p<0.03).
Conclusion:
In term CHD neonates, serial brain metabolism by MRS demonstrates alterations beyond NAA, including neurotransmitters GABA and glutamate/glutamine. These abnormalities are associated with multiple clinical pre and post-op factors and also predict prolonged hospital stay and 18 month ND.
Delayed Cortical Development in Fetuses with Complex Congenital Heart Disease