Cortical Folding Is Altered before Surgery in Infants with Congenital Heart Disease
Open accessAbstract
Infants with congenital heart disease have altered brain development. We characterized cortical folding, a critical part of brain development, in congenital heart disease infants and demonstrated an overall decrease in cortical surface area and cortical folding with regional alterations in the right lateral sulcus and left orbitofrontal region, cingulate region, and central sulcus. These abnormalities were present prior to surgery.
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Less complex sulci are already seen in fetuses with hypoplastic left heart syndrome around 30 weeks' gestation, and cortical folding is diminished in neonates with single ventricle pathology.
“Less complex sulci (delayed first appearance or reduced depth) can already be seen in fetuses with HLHS around 30 weeks' gestation, 38 and cortical folding is diminished in neonates with SVP.38,39,42”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [42]
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“…quantitative magnetic resonance imaging (MRI) techniques and analyses have also revealed early abnormalities in brain metabolism and microstructure, as well as delayed cortical development (Claessens et al., 2016, 2019; Clouchoux et al., 2013; Miller et al., 2007; Ortinau et al., 2013, 2019).”
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“In addition, atypical cortical development has been described in infants with Tetralogy of Fallot, with deeper, broader and more simplistic sulcal patterns.(10) Nevertheless, the increased growth rates in addition to the delayed regional cortical folding emphasize that longitudinal evaluation of cortical folding is re…”
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“In a study describing newborns prior to cardiac surgery, sulcal depth differences were found in the peri‐Sylvian region.(8) Two ultrasound studies in fetuses with a comparable design as ours, but with a smaller sample size,(17,18) showed results that were not in agreement with each other.”
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“Zudem wurden kleinere Hirnvolumina, ein abnormer Hirnstoffwechsel und eine Reduktion der kortikalen Faltung und der Gyralentwicklung sowohl bei Feten [14, 49] als auch bei Neugeborenen mit AHF [65, 66, 74, 85] festgestellt.”
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“…hypoxia has been associated with smaller regional brain volumes and altered white matter and cortical development ( Bonthrone et al., 2021; Cromb et al., 2024; Limperopoulos et al., 2010; Miller et al., 2007; Ng et al., 2020; C. Ortinau et al., 2013; Sun et al., 2015; von Rhein et al., 2015).”
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“…structure in newborns using MRI have also identified developmental lags in total brain volume (von Rhein et al. 2015), gray matter volume (Claessens et al. 2016), and cortical surface area, specifically in regions like the orbitofrontal area, cingulate, and central sulcus (Ortinau et al. 2013).”
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Neuroprotective Strategies – What Do We Really Need to Know?
Guzmán-Pruneda, F. A., & Fraser, C. D. (2014) · Seminars in Thoracic and Cardiovascular Surgery Pediatric Cardiac Surgery Annual · doi:10.1053/j.pcsu.2014.01.005
Linking congenital heart disease and brain functional connectivity in newborns
Asis‐Cruz, J. D., & Limperopoulos, C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817988-8.00024-5
Brain growth in congenital heart disease from prenatal environment to adulthood
Ortinau, C. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817988-8.00025-7
Self-citation(2013) · The Journal of Pediatrics · doi:10.1016/s0022-3476(13)01159-1
Differences in fetal brain development
Shah, E. G., Wilson, S. L., Huang, S. L. B., & Corno, A. F. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-24098-0.00009-8
Schlatterer, S. D., & Smith, J. D. (2025) · Clinics in Perinatology · doi:10.1016/j.clp.2025.02.012
Cortical surface area drives volumetric and cognitive deficits in complex congenital heart diseasePreprint
Toyofuku, A., Ehrler, M., Kretschmar, O., Latal, B., & Tuura, R. (2025) · medRxiv · doi:10.1101/2025.10.09.25337644
“So far, morphometric studies on patients with CHD are relatively scarce, but a few studies have been conducted in fetuses, 5,28 neonates 16,29 and adolescents, 30 which all reported a reduction of total SA without regional predilections, except for one fetal study that reported no CHD-control…”
Intraoperative sodium range affects white matter microstructure in neonatal congenital heart diseasePreprint
van der Meijden, M. E. M., van Loon, K., Nijman, M., Talacua, H., Breur, J. M. P. J., Nijman, J., Claessens, N. H. P., Counsell, S. J., Benders, M. J. N. L., & Bonthrone, A. F. (2025) · medRxiv · doi:10.1101/2025.10.16.25338157
Intraoperative sodium range affects white matter microstructure in neonatal congenital heart disease
van der Meijden, M. E. M., van Loon, K., Nijman, M., Talacua, H., Breur, J. M. P. J., Nijman, J., Claessens, N. H. P., Counsell, S. J., Benders, M. J. N. L., & Bonthrone, A. F. (2026) · International Journal of Cardiology Congenital Heart Disease · doi:10.1016/j.ijcchd.2026.100666
“Altered brain development in CHD originates in utero where altered circulation provides suboptimal cerebral substrate delivery [3], resulting in smaller brain volumes [3] and reduced cortical folding [4] that persists into the neonatal period [5,6].”
Cortical morphology and cognitive impairments in adolescents with complex congenital heart disease
Toyofuku, A., Ehrler, M., Kretschmar, O., Latal, B., & Tuura, R. (2026) · Brain Communications · doi:10.1093/braincomms/fcag124
“So far, morphometric studies on patients with CHD are relatively scarce, but a few studies have been conducted in foetuses, 5,32 neonates 16,33-37 and adolescents.”
Dagur, G., Ortinau, C. M., Chin, T. I., Morris, G., Kleinmahon, J. A., Gurvitz, M. Z., & Bora, S. (2026) · PEDIATRICS · doi:10.1542/peds.2025-071101
Self-citationGal-Er, B., Bonthrone, A. F., Chew, A. T. M., Wilson, S., Cromb, D., Egloff, A. M., Pushparajah, K., Simpson, J. M., van der Meijden, M. E. M., Rutherford, M., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-55283-5
Atypical cortical asymmetries in toddlers with congenital heart disease before surgery
Li, H., Du, X., 程龙献, Yang, F., Ma, S., Lu, F., Zhu, M., Wang, H., Yang, M., & Xuming, M. (2026) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2026.112130
- Authors
- Ortinau, C., Alexopoulos, D., Dierker, D., Van Essen, D., Beca, J., & Inder, T.
- Affiliations
- St. Louis Children's Hospital (US)
- Washington University in St. Louis (US)
- Starship Children's Health (NZ)
- Corresponding author
- Ortinau, Cynthia
- Venue
- The Journal of Pediatrics
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 163
- Issue
- 5
- Pages
- 1507-1510
- ISSN
- 0022-3476 (ISSN-L)
- PMC
- PMC3905308
- OpenAlex
- W2035997475
- Cited by
- 70
- References
- 16
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 2 · 2019: 8 · 2018: 5 · 2017: 10 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 1
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Pediatrics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (KL2TR000450, UL1TR000448)
- National Center for Research Resources (UL1RR024992)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD061619, P30HD062171, T32HD043010)
- Topics
- Health Sciences › Medicine › Epidemiology › Congenital Heart Disease Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- congenital heart disease, cortical folding, brain development, cortical surface area, infants, Sylvian fissure, orbitofrontal cortex, cingulate cortex, central sulcus, neuroanatomical abnormalities
- MeSH terms
- Brain Mapping, Cerebral Cortex, Female, Frontal Lobe, Gyrus Cinguli, Heart Defects, Congenital, Humans, Image Processing, Computer-Assisted, Infant, Newborn, Magnetic Resonance Imaging, Male, Term Birth
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