Delayed cortical gray matter development in neonates with severe congenital heart disease
Open accessAbstract
Background This study aimed to assess cortical gray matter growth and maturation in neonates with congenital heart disease (CHD).Methods Thirty-one (near) term neonates with severe CHD (8 univentricular heart malformation (UVH), 21 d-transposition of great arteries (d-TGA) and 2 aortic coarctation) underwent cerebral MRI before (postnatal-day 7) and after (postnatal-day 24) surgery. Eighteen controls with similar gestational age had one MRI (postnatal-day 23). Cortical gray matter volume (CGM), inner cortical surface (iCS), and median cortical thickness were extracted as measures of volumetric growth, and gyrification index (GI) as measure of maturation.Results Over a median of 18 d, CGM increased by 21%, iCS by 17%, thickness and GI both by 9%. Decreased postoperative CGM and iCS were seen for CHD compared to controls (P values < 0.01), however with similar thickness and GI. UVH showed lower postoperative iCS, thickness (P values < 0.05) and GI (P value < 0.01) than d-TGA and controls. Infants requiring preoperative balloon-atrioseptostomy (BAS, 61%) had reduced postoperative CGM, iCS, and GI (P values < 0.05).Conclusion Infants with severe CHD show reduced cortical volumes compared to controls with gyrification being delayed in UVH, but not in d-TGA. Infants requiring BAS show higher risk of impaired cortical volume and gyrification.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Reductions in brain volumetric growth, cortical folding, and microstructural white matter maturation are well recognized in this high-risk population.
“Additionally, reductions in brain volumetric growth, cortical folding, and microstructural white matter maturation are well recognized in this high-risk population.7,8”
From Perioperative neonatal brain injury is associated with worse school-age neurodevelopment in children with critical congenital heart disease (2018) · cites this paper as [8]
The Postoperative Cortical Morphology Compared to Healthy Controls section reports lower cortical gray matter volume in the CHD infants, supporting a volumetric difference, though it does not establish reduced growth rates relative to controls. The same section reports similar gyrification indices, contrary to a general reduction in cortical folding in this cohort. The paper discusses white matter abnormalities but does not report a measurement of microstructural white matter maturation. (LLM, conf=0.89)
Experimental — accuracy not yet measuredDelayed cortical development, manifesting as delayed cortical folding, cortical depth asymmetry and reduced cortical thickness, has been reported in CHD fetuses and neonates.
“delayed cortical development has been reported in CHD fetuses and neonates; the manifestations include delayed cortical folding, cortical depth asymmetry and reduced cortical thickness (25, 33).”
From Changes in Cortical Thickness Are Associated With Cognitive Ability in Postoperative School-Aged Children With Tetralogy of Fallot (2020) · cites this paper as [33]
The Discussion reports delayed gyrification in neonates with univentricular heart malformations and cites earlier findings of immature cortices in fetuses with hypoplastic left heart syndrome. The Perinatal Risk Factors section reports lower cortical thickness in the univentricular group than in infants with d-TGA, but the Postoperative Cortical Morphology section finds similar thickness in CHD infants and healthy controls and no significant left-right differences in cortical parameters. The paper therefore does not support cortical depth asymmetry or a general reduction in cortical thickness in CHD fetuses and neonates. (LLM, conf=0.90)
Experimental — accuracy not yet measuredNeonates with transposition of the great arteries show a degree of cortical folding comparable to healthy controls.
“Neonates with TGA (n=21) show a comparable degree of cortical folding to healthy controls.39”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [39]
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 [39]
In neonatal studies, white matter and cortical gray matter are comparably reduced in transposition of the great arteries and single ventricle pathology.
“In neonatal studies, white matter and CGM are comparably reduced in TGA and SVP.34,39”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [39]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances
Volpe, J. J. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70294-1 · Cited by 2,420 · see citing works
Abnormal brain development in newborns with congenital heart disease
Miller, S. P., McQuillen, P. S., Hamrick, S., Xu, D., Glidden, D. V., Charlton, N., Karl, T., Azakie, A., Ferriero, D. M., Barkovich, A. J., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa067393 · Cited by 860 · see citing works
Primary cortical folding in the human newborn: an early marker of later functional development
Dubois, J., Benders, M. J. N. L., Borradori-Tolsa, C., Cachia, A., Lazeyras, F., Leuchter, R. H., Sizonenko, S. V., Warfield, S. K., Mangin, J., & Hüppi, P. S. (2008) · Brain · doi:10.1093/brain/awn137 · Cited by 490 · see citing works
Self-citationTolsa, C. B., Zimine, S., Warfield, S. K., Freschi, M., Rossignol, A. S., Lazeyras, F., Hanquinet, S., Rousseil, M. P., & Hüppi, P. S. (2004) · Pediatric Research · doi:10.1203/01.pdr.0000128983.54614.7e · Cited by 483 · see citing works
Mapping the Early Cortical Folding Process in the Preterm Newborn Brain
Dubois, J., Benders, M. J. N. L., Cachia, A., Lazeyras, F., Leuchter, R. H., Sizonenko, S. V., Borradori-Tolsa, C., Mangin, J., & Hüppi, P. S. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhm180 · Cited by 468 · see citing works
Self-citationTemporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects
McQuillen, P. S., Barkovich, A. J., Hamrick, S. E. G., Perez, M., Ward, P., Glidden, D. V., Azakie, A., Karl, T., & Miller, S. P. (2007) · Stroke · doi:10.1161/01.str.0000247941.41234.90 · Cited by 379 · see citing works
Donofrio, M. T., Bremer, Y. A., Schieken, R. M., Gennings, C., Morton, L. D., Eidem, B. W., Cetta, F., Falkensammer, C. B., Huhta, J. C., & Kleinman, C. S. (2003) · Pediatric Cardiology · doi:10.1007/s00246-002-0404-0 · Cited by 364 · see citing works
Brain injury in premature neonates: A primary cerebral dysmaturation disorder?
Back, S. A., & Miller, S. P. (2014) · Annals of Neurology · doi:10.1002/ana.24132 · Cited by 360 · see citing works
Delayed cortical development in fetuses with complex congenital heart disease
Clouchoux, C., du Plessis, A. J., Bouyssi-Kobar, M., Tworetzky, W., McElhinney, D. B., Brown, D. W., Gholipour, A., Kudelski, D., Warfield, S. K., McCarter, R. J., et al. (2013) · Cerebral Cortex · doi:10.1093/cercor/bhs281 · Cited by 309 · see citing works
Impact of congenital heart disease on cerebrovascular blood flow dynamics in the fetus
Kaltman, J. R., Di, H., Tian, Z., & Rychik, J. (2005) · Ultrasound in Obstetrics & Gynecology · doi:10.1002/uog.1785 · Cited by 296 · see citing works
Congenital Brain Anomalies Associated With the Hypoplastic Left Heart Syndrome
Glauser, T. A., RORKE, L. B., Weinberg, P. M., & Clancy, R. R. (1990) · PEDIATRICS · doi:10.1542/peds.85.6.984 · Cited by 270 · see citing works
A Systematic Review of Motor and Cognitive Outcomes After Early Surgery for Congenital Heart Disease
Snookes, S. H., Gunn, J. K., Eldridge, B. J., Donath, S. M., Hunt, R. W., Galea, M. P., & Shekerdemian, L. (2010) · Pediatrics · doi:10.1542/peds.2009-1959 · Cited by 260 · see citing works
McQuillen, P. S., Hamrick, S. E. G., Perez, M. J., Barkovich, A. J., Glidden, D. V., Karl, T. R., Teitel, D., & Miller, S. P. (2006) · Circulation · doi:10.1161/circulationaha.105.566752 · Cited by 253 · see citing works
Brain injury and development in newborns with critical congenital heart disease
Dimitropoulos, A., McQuillen, P. S., Sethi, V., Moosa, A., Chau, V., Xu, D., Brant, R., Azakie, A., Campbell, A., Barkovich, A. J., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e31829bfdcf · Cited by 236 · see citing works
Dean, J. M., McClendon, E., Hansen, K., Azimi-Zonooz, A., Chen, K. Y., Riddle, A., Gong, X., Sharifnia, E., Hagen, M. W., Ahmad, T., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004669 · Cited by 188 · see citing works
Congenital heart disease and brain development
McQuillen, P. S., & Miller, S. P. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05116.x · Cited by 164 · see citing works
Quantitative in vivo MRI measurement of cortical development in the fetus
Clouchoux, C., Kudelski, D., Gholipour, A., Warfield, S. K., Viseur, S., Bouyssi-Kobar, M., Mari, J.-L., Evans, A. C., du Plessis, A. J., & Limperopoulos, C. (2012) · Brain Structure and Function · doi:10.1007/s00429-011-0325-x · Cited by 164 · see citing works
Algra, S. O., Jansen, N. J. G., van der Tweel, I., Schouten, A. N. J., Groenendaal, F., Toet, M., van Oeveren, W., van Haastert, I. C., Schoof, P. H., de Vries, L. S., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.003312 · Cited by 163 · see citing works
Developmental and Functional Outcomes at School Entry in Children with Congenital Heart Defects
Majnemer, A., Limperopoulos, C., Shevell, M. I., Rohlicek, C. V., Rosenblatt, B., & Tchervenkov, C. I. (2008) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2007.12.019 · Cited by 154 · see citing works
Severe Congenital Heart Defects Are Associated with Global Reduction of Neonatal Brain Volumes
von Rhein, M., Buchmann, A., Hagmann, C., Dave, H., Bernet, V., Scheer, I., Knirsch, W., Latal, B., Bernet, V., Bürki, C., et al. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.07.006 · Cited by 128 · see citing works
Self-citationThe vulnerability of the fetal sheep brain to hypoxemia at mid-gestation
Rees, S. M., Stringer, M., Just, Y., Hooper, S. B., & Harding, R. (1997) · Developmental Brain Research · doi:10.1016/s0165-3806(97)81787-7 · Cited by 123 · see citing works
Brain Volume and Neurobehavior in Newborns with Complex Congenital Heart Defects
Owen, M., Shevell, M., Donofrio, M., Majnemer, A., McCarter, R., Vezina, G., Bouyssi-Kobar, M., Evangelou, I., Freeman, D., Weisenfeld, N., et al. (2014) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.11.033 · Cited by 115 · see citing works
Ortinau, C., Beca, J., Lambeth, J., Ferdman, B., Alexopoulos, D., Shimony, J. S., Wallendorf, M., Neil, J., & Inder, T. (2012) · The Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2011.10.039 · Cited by 94 · see citing works
Fetal MRI detects early alterations of brain development in tetralogy of fallot
Schellen, C., Ernst, S., Gruber, G. M., Mlczoch, E., Weber, M., Brugger, P. C., Ulm, B., Langs, G., Salzer-Muhar, U., Prayer, D., et al. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.05.046 · Cited by 79 · see citing works
Development of Cortical Morphology Evaluated with Longitudinal MR Brain Images of Preterm Infants
Moeskops, P., Benders, M. J. N. L., Kersbergen, K. J., Groenendaal, F., de Vries, L. S., Viergever, M. A., & Išgum, I. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131552 · Cited by 76 · see citing works
Self-citationCortical Folding Is Altered before Surgery in Infants with Congenital Heart Disease
Ortinau, C., Alexopoulos, D., Dierker, D., Van Essen, D., Beca, J., & Inder, T. (2013) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.06.045 · Cited by 70 · cited 1× · see citing works
“Articles (23,24) and infants before heart surgery (25).”
Bertholdt, S., Latal, B., Liamlahi, R., Pretre, R., Scheer, I., Goetti, R., Dave, H., Bernet, V., Schmitz, A., von Rhein, M., et al. (2014) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezt422 · Cited by 64 · see citing works
Self-citationZeng, S., Zhou, Q., Zhou, J., Li, M., Long, C., & Peng, Q. (2014) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.14677 · Cited by 64 · see citing works
Impaired Global and Regional Cerebral Perfusion in Newborns with Complex Congenital Heart Disease
Nagaraj, U. D., Evangelou, I. E., Donofrio, M. T., Vezina, L. G., McCarter, R., du Plessis, A. J., & Limperopoulos, C. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.08.004 · Cited by 57 · see citing works
Structural congenital brain disease in congenital heart disease: Results from a fetal MRI program
Mlczoch, E., Brugger, P., Ulm, B., Novak, A., Frantal, S., Prayer, D., & Salzer‐Muhar, U. E. (2012) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2012.07.004 · Cited by 44 · see citing works
Diffusion-Weighted Imaging in Fetuses with Severe Congenital Heart Defects
Berman, J., Hamrick, S. E. G., McQuillen, P. S., Studholme, C., Xu, D., Henry, R. G., Hornberger, L. K., & Glenn, O. A. (2010) · American Journal of Neuroradiology · doi:10.3174/ajnr.a1975 · Cited by 36 · see citing works
Congenital Heart Disease Affects Cerebral Size but Not Brain Growth
Ortinau, C. M., Inder, T. E., Lambeth, J., Wallendorf, M., Finucane, K. A., & Beca, J. (2012) · Pediatric Cardiology · doi:10.1007/s00246-012-0269-9 · Cited by 34 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [19]19. Zeng S, Zhou Q, Zhou J, Li M, Long C, Peng Q. Impaired brain growth of intracranial structures in fetuses with complex congenital heart dis- ease as measured by 3D ultrasonography. Ultrasound Obstet Gynecol 2015;46:174-81.
Cited by
Sorted by citations
Claessens, N. H. P., Algra, S. O., Ouwehand, T. L., Jansen, N. J. G., Schappin, R., Haas, F., Eijsermans, M. J. C., de Vries, L. S., Benders, M. J. N. L., & CHD Lifespan Study Group Utrecht (2018) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.13747 · Cited by 123 · see citing works
Self-citationKelly, C. J., Christiaens, D., Batalle, D., Makropoulos, A., Cordero‐Grande, L., Steinweg, J. K., O'Muircheartaigh, J., Khan, H., Lee, G., Victor, S., et al. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.118.009893 · Cited by 72 · see citing works
Claessens, N. H. P., Kelly, C. J., Counsell, S. J., & Benders, M. J. N. L. (2017) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.13461 · Cited by 59 · see citing works
Self-citationMa, S., Li, Y., Liu, Y., Xu, C., Li, H., Yao, Q., Wang, Y., Yang, Z., Zuo, P., Yang, M., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00691 · Cited by 14 · see citing works
“In addition, delayed cortical development has been reported in CHD fetuses and neonates; the manifestations include delayed cortical folding, cortical depth asymmetry and reduced cortical thickness (25, 33).”
Background
- Authors
- ; on behalf of the Research Group Heart and Brain, Claessens, N. H. P., Moeskops, P., Buchmann, A., Latal, B., Knirsch, W., Scheer, I., Išgum, I., de Vries, L. S., Benders, M. J. N. L., & von Rhein, M.
- Affiliations
- University Medical Center Utrecht (NL)
- University Hospital Zurich (CH)
- University of Zurich (CH)
- Corresponding author
- Benders, Manon J.N.L.
- ORCID
- Venue
- Pediatric Research
- Published
- 2016-07-19
- Volume
- 80
- Issue
- 5
- Pages
- 668-674
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W2497030368
- Cited by
- 66
- References
- 32
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 10 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 1 · 2017: 4 · 2016: 2
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pediatric Research (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- TU/e Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- Else Kröner-Fresenius-Stiftung
- Schweizerische Herzstiftung
- Universitätsspital Zürich
- 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, neonates, brain MRI, d-transposition of the great arteries, coarctation of the aorta, gyrification index, cortical thickness
- MeSH terms
- Aortic Coarctation, Cerebral Cortex, Developmental Disabilities, Female, Heart Defects, Congenital, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Male, Prospective Studies, Risk Factors, Time Factors, Transposition of Great Vessels, Gray Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
