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Original Investigation
April 4, 2016

Association of Prenatal Diagnosis of Critical Congenital Heart Disease With Postnatal Brain Development and the Risk of Brain Injury

Author Affiliations
  • 1Department of Pediatrics, University of California, San Francisco, Benioff Children’s Hospital, San Francisco
  • 2School of Clinical Sciences, University of Bristol and St Michael’s Hospital, Bristol, England
  • 3Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
  • 4Department of Pediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada
  • 5Department of Pediatric Cardiovascular and Thoracic Surgery, University of British Columbia, Vancouver, British Columbia, Canada
  • 6Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada
  • 7Department of Radiology, University of California, San Francisco, Benioff Children’s Hospital, San Francisco
  • 8Department of Neurology, University of California, San Francisco, Benioff Children’s Hospital, San Francisco
JAMA Pediatr. 2016;170(4):e154450. doi:10.1001/jamapediatrics.2015.4450
Abstract

Importance  The relationship of prenatal diagnosis of critical congenital heart disease (CHD) with brain injury and brain development is unknown. Given limited improvement of CHD outcomes with prenatal diagnosis, the effect of prenatal diagnosis on brain health may reveal additional benefits.

Objective  To compare the prevalence of preoperative and postoperative brain injury and the trajectory of brain development in neonates with prenatal vs postnatal diagnosis of CHD.

Design, Setting, and Participants  Cohort study of term newborns with critical CHD recruited consecutively from 2001 to 2013 at the University of California, San Francisco and the University of British Columbia. Term newborns with critical CHD were studied with brain magnetic resonance imaging preoperatively and postoperatively to determine brain injury severity and microstructural brain development with diffusion tensor imaging by measuring fractional anisotropy and the apparent diffusion coefficient. Comparisons of magnetic resonance imaging findings and clinical variables were made between prenatal and postnatal diagnosis of critical CHD. A total of 153 patients with transposition of the great arteries and single ventricle physiology were included in this analysis.

Main Outcomes and Measures  The presence of brain injury on the preoperative brain magnetic resonance imaging and the trajectory of postnatal brain microstructural development.

Results  Among 153 patients (67% male), 96 had transposition of the great arteries and 57 had single ventricle physiology. The presence of brain injury was significantly higher in patients with postnatal diagnosis of critical CHD (41 of 86 [48%]) than in those with prenatal diagnosis (16 of 67 [24%]) (P = .003). Patients with prenatal diagnosis demonstrated faster brain development in white matter fractional anisotropy (rate of increase, 2.2%; 95% CI, 0.1%-4.2%; P = .04) and gray matter apparent diffusion coefficient (rate of decrease, 0.6%; 95% CI, 0.1%-1.2%; P = .02). Patients with prenatal diagnosis had lower birth weight (mean, 3184.5 g; 95% CI, 3050.3-3318.6) than those with postnatal diagnosis (mean, 3397.6 g; 95% CI, 3277.6-3517.6) (P = .02). Those with prenatal diagnosis had an earlier estimated gestational age at delivery (mean, 38.6 weeks; 95% CI, 38.2-38.9) than those with postnatal diagnosis (mean, 39.1 weeks; 95% CI, 38.8-39.5) (P = .03).

Conclusions and Relevance  Newborns with prenatal diagnosis of single ventricle physiology and transposition of the great arteries demonstrate less preoperative brain injury and more robust microstructural brain development than those with postnatal diagnosis. These results are likely secondary to improved cardiovascular stability. The impact of these findings on neurodevelopmental outcomes warrants further study.

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