Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease

Soul, Janet S.; Robertson, Richard L.; Wypij, David; Bellinger, David C.; Visconti, Karen J.; du Plessis, Adré J.; Kussman, Barry D.; Scoppettuolo, Lisa A.; Pigula, Frank; Jonas, Richard A.; Newburger, Jane W.

doi:10.1016/j.jtcvs.2009.02.027

« Previous Next »The Journal of Thoracic and Cardiovascular Surgery
Volume 138, Issue 2 , Pages 374-381, August 2009

Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease

Janet S. Soul, MD, CM
- Department of Neurology, at Children's Hospital Boston, Boston, Mass
- Department of Neurology, at Harvard Medical School, Boston, Mass
- Address for reprints: Janet S. Soul, MD, CM, Department of Neurology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115.
Richard L. Robertson, MD
- Department of Radiology, at Children's Hospital Boston, Boston, Mass
- Department of Radiology, at Harvard Medical School, Boston, Mass
David Wypij, PhD
- Department of Cardiology, at Children's Hospital Boston, Boston, Mass
- Department of Pediatrics, at Harvard Medical School, Boston, Mass
- Department of Biostatistics, Harvard School of Public Health, Boston, Mass
David C. Bellinger, PhD, MSc
- Department of Neurology, at Children's Hospital Boston, Boston, Mass
- Department of Neurology, at Harvard Medical School, Boston, Mass
Karen J. Visconti, PhD
- Department of Cardiovascular Surgery, at Children's Hospital Boston, Boston, Mass
Adré J. du Plessis, MBChB, MPH
- Department of Neurology, at Children's Hospital Boston, Boston, Mass
- Department of Neurology, at Harvard Medical School, Boston, Mass
Barry D. Kussman, MBBCh
- Department of Anesthesiology, at Children's Hospital Boston, Boston, Mass
- Department of Anesthesia, at Harvard Medical School, Boston, Mass
Lisa A. Scoppettuolo, MS
- Department of Cardiology, at Children's Hospital Boston, Boston, Mass
- Department of Biostatistics, Harvard School of Public Health, Boston, Mass
Frank Pigula, MD
- Department of Cardiovascular Surgery, at Children's Hospital Boston, Boston, Mass
- Department of Surgery, at Harvard Medical School, Boston, Mass
Richard A. Jonas, MD
- Department of Cardiovascular Surgery, at Children's Hospital Boston, Boston, Mass
- Department of Surgery, at Harvard Medical School, Boston, Mass
Jane W. Newburger, MD, MPH
- Department of Cardiology, at Children's Hospital Boston, Boston, Mass
- Department of Pediatrics, at Harvard Medical School, Boston, Mass

Received 1 August 2008; received in revised form 13 November 2008; accepted 9 February 2009. published online 13 April 2009.

Objective

Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury.

Methods

Forty-eight infants enrolled in a trial comparing 2 different hematocrits during surgical repair of congenital heart disease underwent brain magnetic resonance imaging scans and neurodevelopmental testing at 1 year of age.

Results

Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional magnetic resonance imaging sequences. Subjects with foci of hemosiderin had a significantly lower Psychomotor Developmental Index at 1 year of age (79.6 ± 16.5, mean ± standard deviation) compared with subjects without these foci (89.5 ± 15.3; P = .04). Older age at surgery and diagnostic group were significantly associated with the presence of hemosiderin foci. Only 1 subject had a small stroke (2%), and 2 subjects had periventricular leukomalacia (4%).

Conclusion

Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in magnetic resonance imaging studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis, and not with risk factors associated with brain injury, in previous studies suggests that the cause and pathogenesis of this abnormality are different from ischemic brain lesions reported previously.

CTSNet classification: 19, 21

Abbreviations and Acronyms: BAS, balloon atrial septostomy, BSID-II, Bayley Scales of Infant Development II, CHD, congenital heart disease, MDI, Mental Development Index, MPGR, multiplanar gradient recalled, PDI, Psychomotor Development Index, PVL, periventricular leukomalacia, TGA, D-transposition of the great arteries, TOF, tetralogy of Fallot, VSD, ventricular septal defect