Brain maturation is delayed in infants with complex congenital heart defects
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Objective Small head circumferences and white matter injury in the form of periventricular leukomalacia have been observed in populations of infants with severe forms of congenital heart defects. This study tests the hypothesis that congenital heart defects delay in utero structural brain development.Methods Full-term infants with hypoplastic left heart syndrome or transposition of the great arteries were prospectively evaluated with preoperative brain magnetic resonance imaging. Patients with independent risk factors for abnormal brain development (shock, end-organ injury, or intrauterine growth retardation) were excluded. Outcome measures included head circumferences and the total maturation score on magnetic resonance imaging. Total maturation score is a previously validated semiquantitative anatomic scoring system used to assess whole brain maturity. The total maturation score evaluates 4 parameters of maturity: (1) myelination, (2) cortical infolding, (3) involution of glial cell migration bands, and (4) presence of germinal matrix tissue.Results The study cohort included 29 neonates with hypoplastic left heart syndrome and 13 neonates with transposition of the great arteries at a mean gestational age of 38.9 +/- 1.1 weeks. Mean head circumference was 1 standard deviation below normal. The mean total maturation score for the cohort was 10.15 +/- 0.94, significantly lower than reported normative data in infants without congenital heart defects, corresponding to a delay of 1 month in structural brain development.Conclusion Before surgery, term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected. This delay in brain development may foster susceptibility to periventricular leukomalacia in the preoperative, intraoperative, and postoperative periods.
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A high prevalence of anatomic and functional neurologic abnormalities has been documented before surgery in newborns with congenital heart disease, and such abnormalities are associated with childhood developmental status.
“Reports from a number of investigators have documented a high prevalence of anatomic and functional neurologic abnormalities prior to surgery in newborns with CHD [9-17], and an association of such abnormalities with childhood developmental status [11,13,18,19].”
From Brain Volume and Metabolism in Fetuses With Congenital Heart Disease: Evaluation With Quantitative Magnetic Resonance Imaging and Spectroscopy (2010) · cites this paper as [17]
Adverse neurodevelopmental outcomes in children with complex congenital heart disease are due not only to perioperative insult but also to inborn factors.
“However, there is increasing evidence that adverse neurodevelopmental outcomes in children with complex CHD are due not only perioperative insult, but to inborn factors as well.”
From Brain Volume and Metabolism in Fetuses With Congenital Heart Disease: Evaluation With Quantitative Magnetic Resonance Imaging and Spectroscopy (2010) · cites this paper as [17]
Prior work has documented that peri-operative brain injury and delayed brain development are common in newborns with CHD.
“Studies have documented a high prevalence of peri-operative brain injury and delayed brain development in neonates with CHD (7–10).”
From Neonatal Brain Injury and Timing of Neurodevelopmental Assessment in Patients With Congenital Heart Disease (2018) · cites this paper as [9]
Similar results appear in human newborns with congenital heart disease, both at autopsy and on brain imaging.
“Similar findings have been observed in human newborns with congenital heart disease (CHD) at autopsy and on brain-imaging studies.[27][28][29][30]”
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 [29]
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Congenital Heart Disease Infant Death Rates Decrease as Gestational Age Advances from 34 to 40 Weeks
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Hypoplastic left heart syndrome: from comfort care to long-term survival
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- Authors
- Licht, D. J., Shera, D. M., Clancy, R. R., Wernovsky, G., Montenegro, L. M., Nicolson, S. C., Zimmerman, R. A., Spray, T. L., Gaynor, J. W., & Vossough, A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Licht, Daniel J.
- ORCID
- Venue
- The Journal of Thoracic and Cardiovascular Surgery
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 137
- Issue
- 3
- Pages
- 529-537
- ISSN
- 0022-5223 (ISSN-L)
- PMC
- PMC2701902
- OpenAlex
- W2105478587
- Cited by
- 629
- References
- 31
- Citations by year
- 2026: 34 · 2025: 30 · 2024: 30 · 2023: 47 · 2022: 40 · 2021: 41 · 2020: 42 · 2019: 49 · 2018: 39 · 2017: 42 · 2016: 49 · 2015: 33 · 2014: 32 · 2013: 30 · 2012: 36
- FWCI
- 20.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic and Cardiovascular Surgery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K23NS052380)
- Topics
- Health Sciences › Medicine › Epidemiology › 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, brain maturation, hypoplastic left heart syndrome, transposition of the great arteries, head circumference, periventricular leukomalacia, white matter injury, germinal matrix, myelination, neonates
- MeSH terms
- Brain, Female, Fetal Growth Retardation, Heart Defects, Congenital, Humans, Infant, Newborn, Male, Prospective Studies, Time Factors, Transposition of Great Vessels, Hypoplastic Left Heart Syndrome
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