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Brain injury and development in newborns with critical congenital heart disease
Open accessAbstract
OBJECTIVE: To determine the relationship between radiologically identifiable brain injuries and delayed brain development as reflected by brain metabolic and microstructural integrity. METHODS: Term newborns with congenital heart disease (CHD) (120 preoperatively and 104 postoperatively) were studied with MRI to determine brain injury severity (BIS), microstructure reflected by fractional anisotropy (FA) and average diffusivity (Dav), and metabolism reflected by N-acetylaspartate (NAA)/choline (Cho) and lactate/Cho. Brain development is characterized by increasing NAA/Cho and white matter FA, and by decreasing Dav and lactate/Cho. RESULTS: Newly acquired brain injury was common (41% preoperative, 30% postoperative). Lower white matter FA (p = 0.005) and lower NAA/Cho (p = 0.01) were associated with increasing preoperative BIS. Higher neonatal illness severity scores (p = 0.03), lower preoperative oxygen saturation (p = 0.002), hypotension (p < 0.001), and septostomy (p = 0.002) were also predictive of higher preoperative BIS. Preoperative FA, Dav, and NAA/Cho did not predict new postoperative BIS. Increasing preoperative BIS predicted higher postoperative Dav (p = 0.002) and lactate/Cho (p = 0.008). Within the postoperative scan, new brain injuries were associated with lower white matter FA (p = 0.04). Postoperative BIS (new lesions) was associated with lower postoperative systolic (p = 0.03) and mean (p = 0.05) blood pressures. CONCLUSIONS: Brain injuries in newborns with CHD are strongly related to abnormalities of brain microstructural and metabolic brain development, especially preoperatively. Both newly acquired preoperative and postoperative brain injuries are related to potentially modifiable clinical risk factors.
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“Accordingly, lower preoperative oxygen saturation and preoperative hypotension are also associated with increased risk of preoperative WMI, 72,74,77,80 as is postnatal diagnosis of the heart defect.59”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [74]
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“Preoperative brain injury is accompanied by decreased microstructural white matter maturation in several studies, 53,55,74 while fetal brain abnormalities are associated with an increased risk of acquired brain injury after birth.85”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [74]
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“Preoperative hypotension and lower preoperative oxygen saturations have been associated with an increased risk of brain injury in infants with CHD.21,25,26”
From Antenatal diagnosis, neonatal brain volumes, and neurodevelopment in transposition of the great arteries (2024) · cites this paper as [25]
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“Impaired fetal brain growth in the setting of CHD results in delayed white matter development, the severity of which is associated with the extent of perinatal WMI, whereas WMI affects subsequent brain maturation.28,42”
From Associations Between Age at Arterial Switch Operation, Brain Growth, and Development in Infants With Transposition of the Great Arteries (2019) · cites this paper as [42]
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“White matter injury (WMI) is described in full-term neonates with CHD with remarkably high incidence.52,59,[74][75][76][77]”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [74]
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“Postoperative WMI is associated with lower mean blood-pressures.71,74,81”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [74]
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“Preoperative neonatal focal infarction is associated with balloon atrioseptostomy in most studies.[72][73][74][75]”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [74]
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Metadata
- Authors
- Dimitropoulos, A., McQuillen, P. S., Sethi, V., Moosa, A., Chau, V., Xu, D., Brant, R., Azakie, A., Campbell, A., Barkovich, A. J., Poskitt, K. J., & Miller, S. P.
- Affiliations
- University of British Columbia (CA)
- ORCID
- Venue
- Neurology
- Published
- 2013-07-16
- Volume
- 81
- Issue
- 3
- Pages
- 241-248
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3770166
- OpenAlex
- W1996831127
- Cited by
- 236
- References
- 39
- Citations by year
- 2026: 16 · 2025: 13 · 2024: 10 · 2023: 22 · 2022: 26 · 2021: 21 · 2020: 22 · 2019: 28 · 2018: 22 · 2017: 15 · 2016: 12 · 2015: 17 · 2014: 10 · 2013: 2
- FWCI
- 9.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (MOP93780)
- National Institute of Neurological Disorders and Stroke (R01NS063876, R01NS40117, P50-NS35902, R01NS040117, P50NS035902)
- National Center for Research Resources (M01RR001271, 5M01RR-01271)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Congenital Heart Disease Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- congenital heart disease, neonatal brain injury, brain development, white matter microstructure, fractional anisotropy, N-acetylaspartate, lactate, brain metabolism, hypoxia, hypotension, septostomy, neonatal surgery, risk factors
- MeSH terms
- Brain Injuries, Female, Heart Defects, Congenital, Humans, Infant, Newborn, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Risk Factors, Anisotropy
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