title: Altered posterior cingulate brain metabolites and cognitive dysfunction in preterm adolescents.
abstract: Extremely preterm (EP, <28 wk gestation) individuals have increased the risk of cognitive deficits compared with controls. The posterior cingulate region has an important role in cognitive function, but how this is affected by preterm birth is unknown. We aimed to compare brain metabolite ratios of neurons and cell membranes between EP 18-y olds and controls, and explore the association between metabolite ratios and cognitive outcomes.
  
  
  
  A regional cohort of 150 EP and 134 controls were recruited for the study. Cerebral metabolites were measured using proton magnetic resonance spectroscopy (MRS) obtained from a left posterior cingulate voxel. Total N-acetylaspartate (tNAA, neuronal marker)/total creatine (tCr), and total choline (tCho, cell membrane marker)/tCr ratios were compared between groups using linear regression. Metabolite ratios were correlated with tests of general intelligence (IQ), memory, and attention using linear or logistic regression.
  
  
  
  Compared with controls, EP had lower tNAA/tCr (mean difference (95% CI) of -2.27% (-4.09, -0.45)) and tCho/tCr (mean difference (95% CI) of -11.11% (-20.37, -1.85)), all P = 0.02. Higher tCho/tCr correlated with better IQ in the EP group only; whereas higher tNAA/tCr ratios correlated with better scores in working memory and attention in both groups.
  
  
  
  EP birth is associated with long-term brain metabolite ratio alterations. This may underlie poorer cognitive performance in EP survivors.
authors.affiliation: Neonatal Services, Royal Women's Hospital, Melbourne, Australia.|Victorian Infant Brain Studies, Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Obstetrics & Gynaecology, University of Melbourne, Melbourne, Australia.
authors.forename: Jeanie L Y
authors.initials: JL
authors.lastname: Cheong
authors.affiliation: University College London Hospitals NHS trust, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Bainbridge
authors.affiliation: Victorian Infant Brain Studies, Murdoch Childrens Research Institute, Melbourne, Australia.|School of Psychological Sciences, University of Melbourne, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Anderson
authors.affiliation: Victorian Infant Brain Studies, Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Victorian Infant Brain Studies, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Burnett
authors.affiliation: Victorian Infant Brain Studies, Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.|Developmental Imaging, Murdoch Childrens Research Institute, Melbourne, Australia.|Florey Institute of Neurosciences and Mental Health, Melbourne, Australia.
authors.forename: Deanne K
authors.initials: DK
authors.lastname: Thompson
authors.affiliation: Victorian Infant Brain Studies, Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.|Royal Children's Hospital, Melbourne, Australia.
authors.forename: Gehan
authors.initials: G
authors.lastname: Roberts
authors.affiliation: School of Psychology, University of Birmingham, Edgbaston, UK.|Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wood
authors.affiliation: Neonatal Services, Royal Women's Hospital, Melbourne, Australia.|Victorian Infant Brain Studies, Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Obstetrics & Gynaecology, University of Melbourne, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Lex W
authors.initials: LW
authors.lastname: Doyle
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Robertson
mesh_terms: D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000097:blood; D001315:Australia; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism; D002794:Choline / Q000097:blood; D003071:Cognition; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000503:physiopathology*; D003404:Creatinine / Q000097:blood; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007234:Infant, Premature; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000502:physiology; D011446:Prospective Studies; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003404:Creatinine; D002794:Choline
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