title: Brain metabolite differences in one-year-old infants born small at term and association with neurodevelopmental outcome.
abstract: OBJECTIVE
  We assessed brain metabolite levels by magnetic resonance spectroscopy (MRS) in 1-year-old infants born small at term, as compared with infants born appropriate for gestational age (AGA), and their association with neurodevelopment at 2 years of age.
  
  
  METHODS
  A total of 40 infants born small (birthweight <10th centile for gestational age) and 30 AGA infants underwent brain MRS at age 1 year on a 3-T scanner. Small-born infants were subclassified as late intrauterine growth restriction or as small for gestational age, based on the presence or absence of prenatal Doppler and birthweight predictors of an adverse perinatal outcome, respectively. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired from the frontal lobe at short echo time. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, Third Edition, assessing cognitive, language, motor, social-emotional, and adaptive behavior scales.
  
  
  RESULTS
  As compared with AGA controls, infants born small showed significantly higher levels of glutamate and total N-acetylaspartate (NAAt) to creatine (Cr) ratio at age 1 year, and lower Bayley Scales of Infant and Toddler Development, Third Edition scores at 2 years. The subgroup with late intrauterine growth restriction further showed lower estimated glutathione levels at age 1 year. Significant correlations were observed for estimated glutathione levels with adaptive scores, and for myo-inositol with language scores. Significant associations were also noticed for NAA/Cr with cognitive scores, and for glutamate/Cr with motor scores.
  
  
  CONCLUSIONS
  Infants born small show brain metabolite differences at 1 year of age, which are correlated with later neurodevelopment. These results support further research on MRS to develop imaging biomarkers of abnormal neurodevelopment.
authors.affiliation: BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Deu, Fetal i+D Fetal Medicine Research Center, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; Fundació Hospital Sant Joan de Déu, Barcelona, Spain. Electronic address: portasferre@clinic.ub.es.
authors.forename: Rui V
authors.initials: RV
authors.lastname: Simões
authors.affiliation: Department of Obstetrics, Maternal-Fetal Medicine Unit, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Cruz-Lemini
authors.affiliation: Department of Radiology Hospital Clinic, Centre de Diagnostic per la Imatge, Hospital Clínic and Medical Image platform, IDIBAPS, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Bargalló
authors.affiliation: BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Deu, Fetal i+D Fetal Medicine Research Center, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Gratacós
authors.affiliation: BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Deu, Fetal i+D Fetal Medicine Research Center, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sanz-Cortés
mesh_terms: D000223:Adaptation, Psychological; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002657:Child Development; D002675:Child, Preschool; D003071:Cognition; D003401:Creatine / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007223:Infant; D007236:Infant, Small for Gestational Age; D007294:Inositol / Q000378:metabolism; D007804:Language Development; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009048:Motor Skills; D066107:Social Skills; D047929:Term Birth
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D005978:Glutathione; D003401:Creatine
keywords: brain metabolism; intrauterine growth restriction; magnetic resonance spectroscopy; small for gestational age