PMID- 35995938 OWN - NLM STAT- MEDLINE DCOM- 20230512 LR - 20230517 IS - 1530-0447 (Electronic) IS - 0031-3998 (Print) IS - 0031-3998 (Linking) VI - 93 IP - 6 DP - 2023 May TI - Neurometabolic changes in neonates with congenital heart defects and their relation to neurodevelopmental outcome. PG - 1642-1650 LID - 10.1038/s41390-022-02253-y [doi] AB - 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 H(1)-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. CI - (c) 2022. The Author(s). FAU - Steger, Celine AU - Steger C AD - Center for MR-Research, University Children's Hospital, Zurich, Switzerland. AD - Pediatric Cardiology, Pediatric Heart Center, Department of Surgery, University Children's Hospital, Zurich, Switzerland. AD - Children's Research Center, University Children's Hospital, Zurich, Switzerland. AD - Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland. AD - University of Zurich, Zurich, Switzerland. FAU - Feldmann, Maria AU - Feldmann M AD - Children's Research Center, University Children's Hospital, Zurich, Switzerland. AD - Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland. AD - University of Zurich, Zurich, Switzerland. AD - Child Development Center, University Children's Hospital, Zurich, Switzerland. FAU - Borns, Julia AU - Borns J AD - Pediatric Cardiology, Pediatric Heart Center, Department of Surgery, University Children's Hospital, Zurich, Switzerland. AD - Children's Research Center, University Children's Hospital, Zurich, Switzerland. AD - Pediatric Cardiology, Inselspital Bern, Bern, Switzerland. FAU - Hagmann, Cornelia AU - Hagmann C AD - Children's Research Center, University Children's Hospital, Zurich, Switzerland. AD - University of Zurich, Zurich, Switzerland. AD - Department of Neonatology and Pediatric Intensive Care, University Children's Hospital, Zurich, Switzerland. FAU - Latal, Beatrice AU - Latal B AD - Children's Research Center, University Children's Hospital, Zurich, Switzerland. AD - University of Zurich, Zurich, Switzerland. AD - Child Development Center, University Children's Hospital, Zurich, Switzerland. FAU - Held, Ulrike AU - Held U AD - University of Zurich, Zurich, Switzerland. AD - Department of Epidemiology, Biostatistics and Prevention Institute UZH, Zurich, Switzerland. FAU - Jakab, Andras AU - Jakab A AD - Center for MR-Research, University Children's Hospital, Zurich, Switzerland. AD - Children's Research Center, University Children's Hospital, Zurich, Switzerland. AD - Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland. AD - University of Zurich, Zurich, Switzerland. FAU - O'Gorman Tuura, Ruth AU - O'Gorman Tuura R AD - Center for MR-Research, University Children's Hospital, Zurich, Switzerland. AD - Children's Research Center, University Children's Hospital, Zurich, Switzerland. AD - Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland. AD - University of Zurich, Zurich, Switzerland. FAU - Knirsch, Walter AU - Knirsch W AUID- ORCID: 0000-0002-8741-3929 AD - Pediatric Cardiology, Pediatric Heart Center, Department of Surgery, University Children's Hospital, Zurich, Switzerland. walter.knirsch@kispi.uzh.ch. AD - Children's Research Center, University Children's Hospital, Zurich, Switzerland. walter.knirsch@kispi.uzh.ch. AD - University of Zurich, Zurich, Switzerland. walter.knirsch@kispi.uzh.ch. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220822 PL - United States TA - Pediatr Res JT - Pediatric research JID - 0100714 RN - MU72812GK0 (Creatine) RN - 3KX376GY7L (Glutamic Acid) RN - 30KYC7MIAI (Aspartic Acid) RN - N91BDP6H0X (Choline) SB - IM MH - Infant, Newborn MH - Infant MH - Humans MH - Magnetic Resonance Spectroscopy MH - *Cerebral Cortex/metabolism MH - Creatine/metabolism MH - Glutamic Acid/metabolism MH - *Heart Defects, Congenital/surgery MH - Aspartic Acid MH - Choline MH - Brain/metabolism PMC - PMC10172141 COIS- The authors declare no competing interests. EDAT- 2022/08/23 06:00 MHDA- 2023/05/12 07:06 PMCR- 2022/08/22 CRDT- 2022/08/22 23:26 PHST- 2022/04/12 00:00 [received] PHST- 2022/07/27 00:00 [accepted] PHST- 2022/07/07 00:00 [revised] PHST- 2023/05/12 07:06 [medline] PHST- 2022/08/23 06:00 [pubmed] PHST- 2022/08/22 23:26 [entrez] PHST- 2022/08/22 00:00 [pmc-release] AID - 10.1038/s41390-022-02253-y [pii] AID - 2253 [pii] AID - 10.1038/s41390-022-02253-y [doi] PST - ppublish SO - Pediatr Res. 2023 May;93(6):1642-1650. doi: 10.1038/s41390-022-02253-y. Epub 2022 Aug 22.