Neurometabolic changes in neonates with congenital heart defects and their relation to neurodevelopmental outcome.

Abstract

Altered neurometabolite ratios in neonates undergoing cardiac surgery for congenital heart defects (CHD) may serve as a biomarker for altered brain development and neurodevelopment (ND). We analyzed single voxel 3T PRESS H¹-MRS data, acquired unilaterally in the left basal ganglia and white matter of 88 CHD neonates before and/or after neonatal cardiac surgery and 30 healthy controls. Metabolite ratios to Creatine (Cr) included glutamate (Glu/Cr), myo-Inositol (mI/Cr), glutamate and glutamine (Glx/Cr), and lactate (Lac/Cr). In addition, the developmental marker N-acetylaspartate to choline (NAA/Cho) was evaluated. All children underwent ND outcome testing using the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) at 1 year of age. White matter NAA/Cho ratios were lower in CHD neonates compared to healthy controls (group beta estimate: -0.26, std. error 0.07, 95% CI: -0.40 - 0.13, p value <0.001, FDR corrected p value = 0.010). We found no correlation between pre- or postoperative white matter NAA/Cho with ND outcome while controlling for socioeconomic status and CHD diagnosis. Reduced white matter NAA/Cho in CHD neonates undergoing cardiac surgery may reflect a delay in brain maturation. Further long-term MRS studies are needed to improve our understanding of the clinical impact of altered metabolites on brain development and outcome. NAA/Cho was reduced in the white matter, but not the gray matter of CHD neonates compared to healthy controls. No correlation to the 1-year neurodevelopmental outcome (Bayley-III) was found. While the rapid change of NAA/Cho with age might make it a sensitive marker for a delay in brain maturation, the relationship to neurodevelopmental outcome requires further investigation.