Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 155 No. 12 (2025)

Serial cerebral magnetic resonance imaging before and after birth in patients with complex congenital heart disease – a prospective, multicentre observational study

Cite this as:
Swiss Med Wkly. 2025;155:4466
Published
02.12.2025

Summary

STUDY AIMS: Our objective was to establish a multicentre foetal-to-neonatal magnetic resonance (MR) neuroimaging programme for neonates undergoing surgery for complex congenital heart disease (CHD). We assessed structural and volumetric MRI findings at different timepoints in various types of CHD and evaluated neurodevelopmental outcomes at one year of age. Additionally, we analysed the feasibility, challenges and limitations of implementing this MR neuroimaging programme.

METHODS: In this prospective, multicentre observational study, we examined brain development and growth in infants with complex CHD requiring neonatal cardiac surgery. Brain MRI was performed at multiple timepoints: at the 32nd week of gestation, after birth (both before and after stage I surgery), and before stage II surgery in single-ventricle CHD. We analysed and compared cardiac diagnoses, treatment approaches, structural and volumetric brain MRI findings and neurodevelopmental outcomes at one year of age (assessed using the Bayley III scale) with those of healthy controls.

RESULTS: Between April 2020 and September 2023, 81 patients and 15 healthy controls underwent at least one MRI. Cardiac diagnoses were biventricular CHD (66.7%), single-ventricle CHD (25.9%) and borderline left ventricle CHD (7.4%). New structural cerebral lesions were found before stage I or after stage I including white matter injury in 3.8% and 8.7%, respectively, ischaemic cerebral lesions in 11.5 and 11.6%, intraventricular haemorrhages in 7.7% and 7.2%, and subdural haemorrhages in 33.6% and 26.1%. Total brain volume at 32.6 (interquartile range [IQR]: 31.3–33.3) gestational weeks was 228.9 ml (213.1–241.2) in biventricular CHD, 194.4 ml (165.3–223.6) in single-ventricle CHD and 196.4 ml (186.4–235.2) in normal healthy controls. After birth, at 6 days (3–16) of life total brain volume was 337.1 ml (310.3–350.2) in biventricular CHD, 331.6 ml (305.9–350.7) in single-ventricle CHD and 406.8 ml (389.9–438.7) in normal healthy controls. After stage I, at 26.5 days (18.3–40.8) total brain volume was 367.7 ml (341.8–385.5) in biventricular CHD, 353.6 ml (338.2–375.7) in single-ventricle CHD and 514.1 ml (482.9–554.6) at 116 days (94.5–118.5) in patients with single-ventricle CHD. At 12.1 months of age, neurodevelopmental performance determined by the Bayley III scale (mean ± SD [standard deviation]) was lower for patients with single-ventricle CHD (cognitive composite score [CCS]: 92.9 ± 13.1; language composite score [LCS]: 88.5 ± 12.0; motor composite score [MCS]: 85.6 ± 14.5) than in patients with biventricular CHD (CCS: 101.2 ± 11.1; LCS: 95.7 ± 13.1; MCS: 87.6 ± 18.0) or in healthy controls (CCS: 113.3 ± 5.6; LCS: 102.3 ± 7.9; MCS: 100.7 ± 8.2). Feasibility for performing cerebral MRI was limited due to maternal/patient safety reasons and further logistical infrastructural reasons.

CONCLUSIONS: Structural cerebral lesions were found at various timepoints in both biventricular and single-ventricle CHD during foetal-to-neonatal serial cerebral MRI. Compared to healthy controls, total brain volume was reduced in patients with complex CHD, and neurodevelopmental outcomes at one year of age were mildly to moderately impaired. Several patient-related and infrastructural challenges limit the feasibility of a routine magnetic resonance neuroimaging programme, necessitating further efforts to optimise its implementation into routine clinical practice in the future.

Trial registration: ClinicalTrials.gov NCT04233775

References

  1. 1. Katz JA, Levy PT, Butler SC, Sadhwani A, Lakshminrusimha S, Morton SU, et al. Preterm congenital heart disease and neurodevelopment: the importance of looking beyond the initial hospitalization. J Perinatol. 2023 Jul;43(7):958–62. doi: https://doi.org/10.1038/s41372-023-01687-4
  2. 2. Agyeman-Duah J, Kennedy S, O’Brien F, Natalucci G. Interventions to improve neurodevelopmental outcomes of children born moderate to late preterm: a systematic review protocol. Gates Open Res. 2021 Sep;5:78. doi: https://doi.org/10.12688/gatesopenres.13246.1
  3. 3. Bora S. Beyond Survival: Challenges and Opportunities to Improve Neurodevelopmental Outcomes of Preterm Birth in Low- and Middle-Income Countries. Clin Perinatol. 2023 Mar;50(1):215–23. doi: https://doi.org/10.1016/j.clp.2022.11.003
  4. 4. De Silvestro A, Reich B, Bless S, Sieker J, Hollander W, de Bijl-Marcus K, et al.; European Association Brain in Congenital Heart Disease. Morbidity and mortality in premature or low birth weight patients with congenital heart disease in three European pediatric heart centers between 2016 and 2020. Front Pediatr. 2024 Apr;12:1323430. doi: https://doi.org/10.3389/fped.2024.1323430
  5. 5. Feldmann M, Bataillard C, Ehrler M, Ullrich C, Knirsch W, Gosteli-Peter MA, et al. Cognitive and Executive Function in Congenital Heart Disease: A Meta-analysis. Pediatrics. 2021 Oct;148(4):e2021050875. doi: https://doi.org/10.1542/peds.2021-050875
  6. 6. Lee FT, Sun L, van Amerom JF, Portnoy S, Marini D, Saini A, et al. Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease. J Am Coll Cardiol. 2024 Apr;83(13):1225–39. doi: https://doi.org/10.1016/j.jacc.2024.02.005
  7. 7. De Silvestro AA, Kellenberger CJ, Gosteli M, O’Gorman R, Knirsch W. Postnatal cerebral hemodynamics in infants with severe congenital heart disease: a scoping review. Pediatr Res. 2023 Sep;94(3):931–43. doi: https://doi.org/10.1038/s41390-023-02543-z
  8. 8. Nijman M, van der Meeren LE, Nikkels PG, Stegeman R, Breur JM, Jansen NJ, et al.; CHD LifeSpan Study Group ‡. Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease. J Am Heart Assoc. 2024 Mar;13(5):e033189. doi: https://doi.org/10.1161/JAHA.123.033189
  9. 9. Homsy J, Zaidi S, Shen Y, Ware JS, Samocha KE, Karczewski KJ, et al. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science. 2015 Dec;350(6265):1262–6. doi: https://doi.org/10.1126/science.aac9396
  10. 10. De Silvestro AA, Krüger B, Steger C, Feldmann M, Payette K, Krüger J, et al. Cerebral desaturation during neonatal congenital heart surgery is associated with perioperative brain structure alterations but not with neurodevelopmental outcome at 1 year. Eur J Cardiothorac Surg. 2022 Oct;62(5):ezac138. doi: https://doi.org/10.1093/ejcts/ezac138
  11. 11. O’Byrne ML, Baxelbaum K, Tam V, Griffis H, Pennington ML, Hagerty A, et al. Association of Postnatal Opioid Exposure and 2-Year Neurodevelopmental Outcomes in Infants Undergoing Cardiac Surgery. J Am Coll Cardiol. 2024 Sep;84(11):1010–21. doi: https://doi.org/10.1016/j.jacc.2024.06.033
  12. 12. Lepage C, Bayard J, Gaudet I, Paquette N, Simard MN, Gallagher A. Parenting stress in infancy was associated with neurodevelopment in 24-month-old children with congenital heart disease. Acta Paediatr. 2025 Jan;114(1):164–72. doi: https://doi.org/10.1111/apa.17421
  13. 13. Lepage C, Bayard J, Gaudet I, Paquette N, Simard MN, Gallagher A. Parenting stress in infancy was associated with neurodevelopment in 24-month-old children with congenital heart disease. Acta Paediatr. 2025 Jan;114(1):164–72. doi: https://doi.org/10.1111/apa.17421
  14. 14. Cassidy AR, Rofeberg V, Bucholz EM, Bellinger DC, Wypij D, Newburger JW. Family Socioeconomic Status and Neurodevelopment Among Patients With Dextro-Transposition of the Great Arteries. JAMA Netw Open. 2024 Nov;7(11):e2445863. doi: https://doi.org/10.1001/jamanetworkopen.2024.45863
  15. 15. Sun L, Macgowan CK, Sled JG, Yoo SJ, Manlhiot C, Porayette P, et al. Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation. 2015 Apr;131(15):1313–23. doi: https://doi.org/10.1161/CIRCULATIONAHA.114.013051
  16. 16. Ortinau CM, Mangin-Heimos K, Moen J, Alexopoulos D, Inder TE, Gholipour A, et al. Prenatal to postnatal trajectory of brain growth in complex congenital heart disease. Neuroimage Clin. 2018;20:913–22. doi: https://doi.org/10.1016/j.nicl.2018.09.029
  17. 17. Phillips K, Callaghan B, Rajagopalan V, Akram F, Newburger JW, Kasparian NA. Neuroimaging and Neurodevelopmental Outcomes Among Individuals With Complex Congenital Heart Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Dec;82(23):2225–45. doi: https://doi.org/10.1016/j.jacc.2023.09.824
  18. 18. Ottolenghi S, Milano G, Cas MD, Findley TO, Paroni R, Corno AF. Can Erythropoietin Reduce Hypoxemic Neurological Damages in Neonates With Congenital Heart Defects? Front Pharmacol. 2021 Nov;12:770590. doi: https://doi.org/10.3389/fphar.2021.770590
  19. 19. Natterer J, Schneider J, Sekarski N, Rathke V, Adams M, Latal B, et al. ORCHID (Outcome Registry for CHIldren with severe congenital heart Disease) a Swiss, nationwide, prospective, population-based, neurodevelopmental paediatric patient registry: framework, regulations and implementation. Swiss Med Wkly. 2022 Sep;152(3536):w30217. doi: https://doi.org/10.4414/SMW.2022.w30217
  20. 20. Feldmann M, Hagmann C, de Vries L, Disselhoff V, Pushparajah K, Logeswaran T, et al. Neuromonitoring, neuroimaging, and neurodevelopmental follow-up practices in neonatal congenital heart disease: a European survey. Pediatr Res. 2023 Jan;93(1):168–75. doi: https://doi.org/10.1038/s41390-022-02063-2
  21. 21. Stegeman R, Feldmann M, Claessens NH, Jansen NJ, Breur JM, de Vries LS, et al.; European Association Brain in Congenital Heart Disease Consortium. A Uniform Description of Perioperative Brain MRI Findings in Infants with Severe Congenital Heart Disease: results of a European Collaboration. AJNR Am J Neuroradiol. 2021 Nov;42(11):2034–9. doi: https://doi.org/10.3174/ajnr.A7328
  22. 22. Kuklisova-Murgasova M, Quaghebeur G, Rutherford MA, Hajnal JV, Schnabel JA. Reconstruction of fetal brain MRI with intensity matching and complete outlier removal. Med Image Anal. 2012 Dec;16(8):1550–64. doi: https://doi.org/10.1016/j.media.2012.07.004
  23. 23. Meuwly E, Feldmann M, Knirsch W, von Rhein M, Payette K, Dave H, et al.; Research Group Heart and Brain*. Postoperative brain volumes are associated with one-year neurodevelopmental outcome in children with severe congenital heart disease. Sci Rep. 2019 Jul;9(1):10885. doi: https://doi.org/10.1038/s41598-019-47328-9
  24. 24. Bayley, N. 3rd ed. Bayley Scales of Infant and Toddler Development Manual; 2006.
  25. 25. Dubowitz L, Dubowitz V. The neurologic assessment of the preterm and full-term newborn infant. Clinics in Developmental Medicine. London, UK: Spastics International Medical Publications/William Heinemann Medical Books; 1981.
  26. 26. Haataja L, Mercuri E, Regev R, Cowan F, Rutherford M, Dubowitz V, et al. Optimality score for the neurologic examination of the infant at 12 and 18 months of age. J Pediatr. 1999 Aug;135(2 Pt 1):153–61. doi: https://doi.org/10.1016/S0022-3476(99)70016-8
  27. 27. Latal B. Neurodevelopmental Outcomes of the Child with Congenital Heart Disease. Clin Perinatol. 2016 Mar;43(1):173–85. doi: https://doi.org/10.1016/j.clp.2015.11.012
  28. 28. McQuillen PS, Miller SP. Congenital heart disease and brain development. Ann N Y Acad Sci. 2010 Jan;1184(1):68–86. doi: https://doi.org/10.1111/j.1749-6632.2009.05116.x
  29. 29. Juergensen S, Liu J, Xu D, Zhao Y, Moon-Grady AJ, Glenn O, et al. Fetal circulatory physiology and brain development in complex congenital heart disease: A multi-modal imaging study. Prenat Diagn. 2024 Jun;44(6-7):856–64. doi: https://doi.org/10.1002/pd.6450
  30. 30. Sadhwani A, Wypij D, Rofeberg V, Gholipour A, Mittleman M, Rohde J, et al. Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease. Circulation. 2022 Apr;145(15):1108–19. doi: https://doi.org/10.1161/CIRCULATIONAHA.121.056305
  31. 31. Sien ME, Robinson AL, Hu HH, Nitkin CR, Hall AS, Files MG, et al. Feasibility of and experience using a portable MRI scanner in the neonatal intensive care unit. Arch Dis Child Fetal Neonatal Ed. 2023 Jan;108(1):45–50. doi: https://doi.org/10.1136/archdischild-2022-324200
  32. 32. Neukomm A, Claessens NH, Bonthrone AF, Stegeman R, Feldmann M, Nijman M, et al.; European Association Brain in Congenital Heart Disease (EU-ABC) consortium. Perioperative Brain Injury in Relation to Early Neurodevelopment Among Children with Severe Congenital Heart Disease: results from a European Collaboration. J Pediatr. 2024 Mar;266:113838. doi: https://doi.org/10.1016/j.jpeds.2023.113838
  33. 33. Bonthrone AF, Stegeman R, Feldmann M, Claessens NH, Nijman M, Jansen NJ, et al. Risk Factors for Perioperative Brain Lesions in Infants With Congenital Heart Disease: A European Collaboration. Stroke. 2022 Dec;53(12):3652–61. doi: https://doi.org/10.1161/STROKEAHA.122.039492
  34. 34. Barzilay E, Bar-Yosef O, Dorembus S, Achiron R, Katorza E. Fetal Brain Anomalies Associated with Ventriculomegaly or Asymmetry: An MRI-Based Study. AJNR Am J Neuroradiol. 2017 Feb;38(2):371–5. doi: https://doi.org/10.3174/ajnr.A5009
  35. 35. Pappalardo EM, Militello M, Rapisarda G, Imbruglia L, Recupero S, Ermito S, et al. Fetal intracranial cysts: prenatal diagnosis and outcome. J Prenat Med. 2009 Apr;3(2):28–30.
  36. 36. Miller SP, McQuillen PS, Hamrick S, Xu D, Glidden DV, Charlton N, et al. Abnormal brain development in newborns with congenital heart disease. N Engl J Med. 2007 Nov;357(19):1928–38. doi: https://doi.org/10.1056/NEJMoa067393
  37. 37. Dijkhuizen EI, de Munck S, de Jonge RC, Dulfer K, van Beynum IM, Hunfeld M, et al. Early brain magnetic resonance imaging findings and neurodevelopmental outcome in children with congenital heart disease: A systematic review. Dev Med Child Neurol. 2023 Dec;65(12):1557–72. doi: https://doi.org/10.1111/dmcn.15588
  38. 38. Peyvandi S, Xu D, Barkovich AJ, Gano D, Chau V, Reddy VM, et al. Declining Incidence of Postoperative Neonatal Brain Injury in Congenital Heart Disease. J Am Coll Cardiol. 2023 Jan;81(3):253–66. doi: https://doi.org/10.1016/j.jacc.2022.10.029
  39. 39. Schellen C, Ernst S, Gruber GM, Mlczoch E, Weber M, Brugger PC, et al. Fetal MRI detects early alterations of brain development in Tetralogy of Fallot. Am J Obstet Gynecol. 2015 Sep;213(3):392.e1–7. doi: https://doi.org/10.1016/j.ajog.2015.05.046
  40. 40. Ortinau CM, Wypij D, Ilardi D, Rofeberg V, Miller TA, Donohue J, et al. Factors Associated With Attendance for Cardiac Neurodevelopmental Evaluation. Pediatrics. 2023 Sep;152(3):e2022060995. doi: https://doi.org/10.1542/peds.2022-060995
  41. 41. Gaynor JW, Stopp C, Wypij D, Andropoulos DB, Atallah J, Atz AM, et al.; International Cardiac Collaborative on Neurodevelopment (ICCON) Investigators. Neurodevelopmental outcomes after cardiac surgery in infancy. Pediatrics. 2015 May;135(5):816–25. doi: https://doi.org/10.1542/peds.2014-3825
  42. 42. Selvanathan T, Mabbott C, Au-Young SH, Seed M, Miller SP, Chau V; PCNR Study Group. Antenatal diagnosis, neonatal brain volumes, and neurodevelopment in transposition of the great arteries. Dev Med Child Neurol. 2024 Jul;66(7):882–91. doi: https://doi.org/10.1111/dmcn.15840
  43. 43. Wilson S, Cromb D, Bonthrone AF, Uus A, Price A, Egloff A, et al. Structural Covariance Networks in the Fetal Brain Reveal Altered Neurodevelopment for Specific Subtypes of Congenital Heart Disease. J Am Heart Assoc. 2024 Nov;13(21):e035880. doi: https://doi.org/10.1161/JAHA.124.035880
  44. 44. Rowlands MA, Scheinost D, Lacadie C, Vohr B, Li F, Schneider KC, et al. Language at rest: A longitudinal study of intrinsic functional connectivity in preterm children. Neuroimage Clin. 2016 Jan;11:149–57. doi: https://doi.org/10.1016/j.nicl.2016.01.016
  45. 45. Young JM, Morgan BR, Whyte HE, Lee W, Smith ML, Raybaud C, et al.; Longitudinal Study of White Matter Development and Outcomes in Children Born Very Preterm. Longitudinal Study of White Matter Development and Outcomes in Children Born Very Preterm. Cereb Cortex. 2017 Aug;27(8):4094–105.
  46. 46. Variane GF, Chock VY, Netto A, Pietrobom RF, Van Meurs KP. Simultaneous Near-Infrared Spectroscopy (NIRS) and Amplitude-Integrated Electroencephalography (aEEG): Dual Use of Brain Monitoring Techniques Improves Our Understanding of Physiology. Front Pediatr. 2020 Jan;7:560. doi: https://doi.org/10.3389/fped.2019.00560
  47. 47. Chiperi LE, Tecar C, Toganel R. Neuromarkers which can predict neurodevelopmental impairment among children with congenital heart defects after cardiac surgery: A systematic literature review. Dev Neurorehabil. 2023 Apr;26(3):206–15. doi: https://doi.org/10.1080/17518423.2023.2166618