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Original Article
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Volume 357:1928-1938 November 8, 2007 Number 19
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Abnormal Brain Development in Newborns with Congenital Heart Disease
Steven P. Miller, M.D., C.M., Patrick S. McQuillen, M.D., Shannon Hamrick, M.D., Duan Xu, Ph.D., David V. Glidden, Ph.D., Natalie Charlton, B.S., Tom Karl, M.D., Anthony Azakie, M.D., Donna M. Ferriero, M.D., A. James Barkovich, M.D., and Daniel B. Vigneron, Ph.D.

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ABSTRACT

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.


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From the Departments of Neurology (S.P.M., D.M.F., A.J.B.), Pediatrics (P.S.M., D.M.F., A.J.B.), Radiology (D.X., N.C., A.J.B., D.B.V.), Epidemiology and Biostatistics (D.V.G.), and Surgery (T.K., A.A.), University of California at San Francisco, San Francisco; the Department of Pediatrics, University of British Columbia, Vancouver, Canada (S.P.M.); and the Department of Pediatrics, Emory University, Atlanta (S.H.).

Address reprint requests to Dr. Miller at the Division of Neurology, BC Children's Hospital, K3-180, 4480 Oak St., Vancouver, BC V6H 3V4, Canada, or at smiller6{at}cw.bc.ca.

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