Impaired neuroanatomic development in infants with congenital heart disease

doi:10.1016/j.jtcvs.2008.06.036

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Impaired neuroanatomic development in infants with congenital heart disease

Kazuhiro Watanabe, MD^a, Mie Matsui, MD^b, Junko Matsuzawa, MD^a, Chiaki Tanaka, MD^a, Kyo Noguchi, MD^c, Naoki Yoshimura, MD^d, Kazuhisa Hongo, MD^a, Mayumi Ishiguro, PhD^b, Sayaka Wanatabe, MD^a, Keiich Hirono, MD^a, Keiichiro Uese, MD^a, Fukiko Ichida, MD^a^,_*, Hideki Origasa, PhD^e, Jun Nakazawa, MD^f, Yoshihiro Oshima, MD^g, Toshio Miyawaki, MD^a, Tachiyo Matsuzaki, PhD^h, Toshikatsu Yagihara, MD^h, Warren Bilker, PhDⁱ, Ruben C. Gur, MD^j

^a Department of Pediatrics, University of Toyama, Toyama, Japan
^b Department of Psychology, University of Toyama, Toyama, Japan
^c Department of Radiology, University of Toyama, Toyama, Japan
^d Department of Cardiothoracic Surgery, University of Toyama, Toyama, Japan
^e Division of Biostatistics, University of Toyama, Toyama, Japan
^f Department of Psychology, Chiba University, Chiba, Japan
^g Department of Cardiothoracic Surgery, Hyogo Children's Hospital, Kobe, Japan
^h Department of Cardiothoracic Surgery, National Cardiovascular Center, Osaka, Japan
ⁱ Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pa
^j Department of Psychiatry, University of Pennsylvania, Philadelphia, Pa

Received for publication March 23, 2008; revisions received May 29, 2008; accepted for publication June 24, 2008.

^_* Address for reprints: Fukiko Ichida, MD, Department of Pediatrics, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194 Japan. (Email: fukiko{at}med.u-toyama.ac.jp).

Objectives: We performed a regional volumetric study of the brain using3-dimensional magnetic resonance imaging in infants with congenitalheart disease to search for variables in anatomic developmentof the brain that may be associated with functional impairment.

Methods: Forty infants with congenital heart disease—17 infantswith single ventricle physiology, 5 with transposition of greatarteries, and 18 with ventricular septal defect—were studiedprospectively by 3-dimensional magnetic resonance imaging ofthe brain several months after heart surgery.

Results: The global volume of gray matter was significantly reduced inthe patients with congenital heart disease compared with normalcontrols (P < .001), whereas no significant difference inthe volume of white matter was observed. Further, the decreasein gray matter volume was more apparent in the frontal lobethan in the temporal lobe, especially in infants with singleventricle physiology or transposition of the great arteries.Multivariate analysis revealed that preoperative hypoxia isstrongly associated with decreased frontal gray matter volume(P < .01), as well as a diagnosis of hypoplastic left heartsyndrome (P < .05). Of note, frontal gray matter volume,which includes the motor area, correlated weakly with psychomotordevelopmental index scores (P < .01).

Conclusions: Brain developmental impairment occurs in many infants with congenitalheart disease, especially in those who have preoperative hypoxiaand critical congenital heart disease. This quantitative volumetricstudy encourages larger scale and longitudinal follow-up toelucidate the significance of impaired neuroanatomic developmenton functional outcome.

Abbreviations and Acronyms CHD = congenital heart disease; CSF= cerebrospinal fluid; 3D-MRI = 3-dimensional magnetic resonanceimaging; GM = gray matter; HLHS = hypoplastic left heart syndrome;MDI = mental developmental index; MRI = magnetic resonance imaging;PDI = psychomotor developmental index; SV = single ventricle;TGA = transposition of the great arteries; VSD = ventricularseptal defect; WM = white matter

Congenital Heart Disease

Impaired neuroanatomic development in infants with congenital heart disease