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

Pediatr Res. 2023 May;93(6):1642-1650. doi: 10.1038/s41390-022-02253-y. Epub 2022 Aug 22.

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Impact: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid
  • Brain / metabolism
  • Cerebral Cortex* / metabolism
  • Choline
  • Creatine / metabolism
  • Glutamic Acid / metabolism
  • Heart Defects, Congenital* / surgery
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Spectroscopy

Substances

  • Creatine
  • Glutamic Acid
  • Aspartic Acid
  • Choline