title: Brain volume and metabolism in fetuses with congenital heart disease: evaluation with quantitative magnetic resonance imaging and spectroscopy.
abstract: BACKGROUND
  Adverse neurodevelopmental outcome is an important source of morbidity in children with congenital heart disease (CHD). A significant proportion of newborns with complex CHD have abnormalities of brain size, structure, or function, which suggests that antenatal factors may contribute to childhood neurodevelopmental morbidity.
  
  
  RESULTS
  Brain volume and metabolism were compared prospectively between 55 fetuses with CHD and 50 normal fetuses with the use of 3-dimensinal volumetric magnetic resonance imaging and proton magnetic resonance spectroscopy. Fetal intracranial cavity volume, cerebrospinal fluid volume, and total brain volume were measured by manual segmentation. Proton magnetic resonance spectroscopy was used to measure the cerebral N-acetyl aspartate: choline ratio (NAA:choline) and identify cerebral lactate. Complete fetal echocardiograms were performed. Gestational age at magnetic resonance imaging ranged from 25 1/7 to 37 1/7 weeks (median, 30 weeks). During the third trimester, there were progressive and significant declines in gestational age-adjusted total brain volume and intracranial cavity volume in CHD fetuses relative to controls. NAA:choline increased progressively over the third trimester in normal fetuses, but the rate of rise was significantly slower (P<0.001) in CHD fetuses. On multivariable analysis adjusted for gestational age and weight percentile, cardiac diagnosis and percentage of combined ventricular output through the aortic valve were independently associated with total brain volume. Independent predictors of lower NAA:choline included diagnosis, absence of antegrade aortic arch flow, and evidence of cerebral lactate (P<0.001).
  
  
  CONCLUSIONS
  Third-trimester fetuses with some forms of CHD have smaller gestational age- and weight-adjusted total brain volumes than normal fetuses and evidence of impaired neuroaxonal development and metabolism. Hemodynamic factors may play an important role in this abnormal development.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. catherine.limperopoulos@mcgill.ca
authors.forename: Catherine
authors.initials: C
authors.lastname: Limperopoulos
authors.forename: Wayne
authors.initials: W
authors.lastname: Tworetzky
authors.forename: Doff B
authors.initials: DB
authors.lastname: McElhinney
authors.forename: Jane W
authors.initials: JW
authors.lastname: Newburger
authors.forename: David W
authors.initials: DW
authors.lastname: Brown
authors.forename: Richard L
authors.initials: RL
authors.lastname: Robertson
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guizard
authors.forename: Ellen
authors.initials: E
authors.lastname: McGrath
authors.forename: Judith
authors.initials: J
authors.lastname: Geva
authors.forename: David
authors.initials: D
authors.lastname: Annese
authors.forename: Carolyn
authors.initials: C
authors.lastname: Dunbar-Masterson
authors.forename: Bethany
authors.initials: B
authors.lastname: Trainor
authors.forename: Peter C
authors.initials: PC
authors.lastname: Laussen
authors.forename: Adré J
authors.initials: AJ
authors.lastname: du Plessis
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D011522:Protons
chemical_list: D011522:Protons; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D002794:Choline