Abnormal brain development in newborns with congenital heart disease.

BACKGROUND Congenital heart disease in newborns is associated with global impairment in development. We characterized brain metabolism and microstructure, as measures of brain maturation, in newborns with congenital heart disease before they underwent heart surgery. METHODS We studied 41 term newborns with congenital heart disease--29 who had transposition of the great arteries and 12 who had single-ventricle physiology--with the use of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) before cardiac surgery. We calculated the ratio of N-acetylaspartate to choline (which increases with brain maturation), the ratio of lactate to choline (which decreases with maturation), average diffusivity (which decreases with maturation), and fractional anisotropy of white-matter tracts (which increases with maturation). We compared these findings with those in 16 control newborns of a similar gestational age. RESULTS As compared with control newborns, those with congenital heart disease had a decrease of 10% in the ratio of N-acetylaspartate to choline (P=0.003), an increase of 28% in the ratio of lactate to choline (P=0.08), an increase of 4% in average diffusivity (P<0.001), and a decrease of 12% in white-matter fractional anisotropy (P<0.001). Preoperative brain injury, as seen on MRI, was not significantly associated with findings on MRS or DTI. White-matter injury was observed in 13 newborns with congenital heart disease (32%) and in no control newborns. CONCLUSIONS Term newborns with congenital heart disease have widespread brain abnormalities before they undergo cardiac surgery. The imaging findings in such newborns are similar to those in premature newborns and may reflect abnormal brain development in utero.

[1]  Steven P. Miller,et al.  Pyramidal tract maturation after brain injury in newborns with heart disease , 2006, Annals of neurology.

[2]  W. Webb,et al.  Neural Activity Triggers Neuronal Oxidative Metabolism Followed by Astrocytic Glycolysis , 2004, Science.

[3]  C. Shatz,et al.  Selective Vulnerability of Subplate Neurons after Early Neonatal Hypoxia-Ischemia , 2003, The Journal of Neuroscience.

[4]  David V Glidden,et al.  Temporal and Anatomic Risk Profile of Brain Injury With Neonatal Repair of Congenital Heart Defects , 2007, Stroke.

[5]  B. Herpertz-Dahlmann,et al.  Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries , 2002, Archives of disease in childhood.

[6]  Steven P. Miller,et al.  Serial quantitative diffusion tensor MRI of the premature brain: Development in newborns with and without injury , 2002, Journal of magnetic resonance imaging : JMRI.

[7]  Josh Star-Lack,et al.  In VivoLactate Editing with Simultaneous Detection of Choline, Creatine, NAA, and Lipid Singlets at 1.5 T Using PRESS Excitation with Applications to the Study of Brain and Head and Neck Tumors☆ , 1998 .

[8]  J. Cuzick,et al.  A Wilcoxon-type test for trend. , 1985, Statistics in medicine.

[9]  J. Volpe Neurology of the Newborn , 1959, Major problems in clinical pediatrics.

[10]  G. Gamkrelidze,et al.  Developmental Changes in Diffusion Anisotropy Coincide with Immature Oligodendrocyte Progression and Maturation of Compound Action Potential , 2005, The Journal of Neuroscience.

[11]  D B Vigneron,et al.  The Normal Neonatal Brain: MR Imaging, Diffusion Tensor Imaging, and 3D MR Spectroscopy in Healthy Term Neonates , 2007, American Journal of Neuroradiology.

[12]  G. Marx,et al.  Aortic valvuloplasty in the fetus: technical characteristics of successful balloon dilation. , 2005, The Journal of pediatrics.

[13]  A. Benachi,et al.  Middle cerebral artery Doppler in fetuses with transposition of the great arteries , 2002, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[14]  C. Gennings,et al.  Autoregulation of Cerebral Blood Flow in Fetuses with Congenital Heart Disease: The Brain Sparing Effect , 2003, Pediatric Cardiology.

[15]  A. Snyder,et al.  Radial organization of developing preterm human cerebral cortex revealed by non-invasive water diffusion anisotropy MRI. , 2002, Cerebral cortex.

[16]  D. Larkman,et al.  Axial and Radial Diffusivity in Preterm Infants Who Have Diffuse White Matter Changes on Magnetic Resonance Imaging at Term-Equivalent Age , 2006, Pediatrics.

[17]  Robert A. Zimmerman,et al.  An MRI Study of Neurological Injury Before and After Congenital Heart Surgery , 2002, Circulation.

[18]  J. Hoffman,et al.  The incidence of congenital heart disease. , 2002, Journal of the American College of Cardiology.

[19]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[20]  Steven P. Miller,et al.  MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy. , 2006, AJNR. American journal of neuroradiology.

[21]  A. Rudolph,et al.  Congenital Diseases of the Heart: Clinical-Physiological Considerations , 2001 .

[22]  Steven P. Miller,et al.  Preoperative brain injury in newborns with transposition of the great arteries. , 2004, The Annals of thoracic surgery.

[23]  Ucsf Medical Balloon atrial septostomy is associated with preoperative stroke in neonates with transposition of the great arteries , 2006 .

[24]  A. Snyder,et al.  Diffusion-tensor MR imaging of gray and white matter development during normal human brain maturation. , 2002, AJNR. American journal of neuroradiology.

[25]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[26]  J GironaComas Congenital diseases of the heart: clinical-physiological considerations , 2001 .

[27]  Hua Jin,et al.  Comparing microstructural and macrostructural development of the cerebral cortex in premature newborns: Diffusion tensor imaging versus cortical gyration , 2005, NeuroImage.

[28]  Roland G. Henry,et al.  Diffusion tensor imaging: serial quantitation of white matter tract maturity in premature newborns , 2004, NeuroImage.

[29]  T. Inder Early Brain Injury in Premature Newborns Detected With Magnetic Resonance Imaging Is Associated With Adverse Early Neurodevelopmental Outcome , 2007 .

[30]  B. Rosenblatt,et al.  Functional limitations in young children with congenital heart defects after cardiac surgery. , 2001, Pediatrics.

[31]  Jeffrey J. Kelly,et al.  Spatial Heterogeneity in Oligodendrocyte Lineage Maturation and Not Cerebral Blood Flow Predicts Fetal Ovine Periventricular White Matter Injury , 2006, The Journal of Neuroscience.

[32]  Steven P. Miller,et al.  Predictors of 30-Month Outcome after Perinatal Depression: Role of Proton MRS and Socioeconomic Factors , 2002, Pediatric Research.

[33]  Gregory L. Holmes,et al.  Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. , 1995, The New England journal of medicine.

[34]  F. Campbell Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass, Bellinger DC, Jonas RA, Rappaport LA, in: N Engl J Med, 332. (1995), 549 , 1995 .

[35]  D B Vigneron,et al.  Three-dimensional proton MR spectroscopic imaging of premature and term neonates. , 2001, AJNR. American journal of neuroradiology.

[36]  D. Richardson,et al.  Birth weight and illness severity: independent predictors of neonatal mortality. , 1993, Pediatrics.

[37]  Gil Wernovsky,et al.  Periventricular leukomalacia is common after neonatal cardiac surgery. , 2004, The Journal of thoracic and cardiovascular surgery.

[38]  P. Weinberg,et al.  Congenital brain anomalies associated with the hypoplastic left heart syndrome. , 1990, Pediatrics.

[39]  J Star-Lack,et al.  In vivo lactate editing with simultaneous detection of choline, creatine, NAA, and lipid singlets at 1.5 T using PRESS excitation with applications to the study of brain and head and neck tumors. , 1998, Journal of magnetic resonance.

[40]  C Boesch,et al.  Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy , 2002, Magnetic resonance in medicine.

[41]  D. Vigneron,et al.  Magnetic resonance imaging compatible neonate incubator , 2002 .

[42]  D. Vigneron Magnetic resonance spectroscopic imaging of human brain development. , 2006, Neuroimaging clinics of North America.

[43]  Arterial switch with full-flow cardiopulmonary bypass and limited circulatory arrest: neurodevelopmental outcome. , 2004 .

[44]  Gil Wernovsky,et al.  Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. , 2003, The Journal of thoracic and cardiovascular surgery.

[45]  P. Albert,et al.  Models for longitudinal data: a generalized estimating equation approach. , 1988, Biometrics.

[46]  T. Inder,et al.  Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. , 2006, The New England journal of medicine.

[47]  Steven P. Miller,et al.  Patterns of brain injury in term neonatal encephalopathy. , 2005, The Journal of pediatrics.

[48]  H. Kinney,et al.  Hypoxic-ischemic brain injury in infants with congenital heart disease dying after cardiac surgery , 2005, Acta Neuropathologica.

[49]  Catherine Limperopoulos,et al.  Predictors of developmental disabilities after open heart surgery in young children with congenital heart defects. , 2002, The Journal of pediatrics.

[50]  D G Altman,et al.  Statistics Notes: Logarithms , 1996, BMJ.

[51]  J. Kucharczyk,et al.  Visualization of nonstructural changes in early white matter development on diffusion-weighted MR images: evidence supporting premyelination anisotropy. , 2001, AJNR. American journal of neuroradiology.