Best Papers – Brain Development and Neurodevelopment and Congenital Heart Disease

The Best Paper selections have been divided into 2 topics:

Brain Development and Congenital Heart Disease

Neurodevelopment and Congenital Heart Disease

These articles were selected by Dr. Gary Webb (Cincinnati); Dr. Ginnie Abarbanell (Atlanta); and Dr. Shaji Menon (Salt Lake City). The take-home points were provided by Drs. Abarbanell and Menon.

Dr. Gary Webb

Dr. Ginnie Abarbanell

Dr. Shaji Menon Brain


Neurodevelopmental delay with critical congenital heart disease is mainly from prenatal injury not infant cardiac surgery: current evidence based on a meta-analysis of functional magnetic resonance imaging.

Li Y, Yin S, Fang J, Hua Y, Wang C, Mu D, Zhou K – Ultrasound Obstetrics and Gynecology 45; 69-648, 2015

Take Home Points:

  1. Cardiac surgery and cardiopulmonary bypass caused a certain amount of injury to the brain and disturbed its metabolism, but only for a short time.
  2. The neurodevelopmental delay in cases of critical CHD was a result of abnormal fetal hemodynamics, suggesting that the origin of such injury was mainly preoperative.
  3. Treatment for cerebral protection during both pregnancy and surgery is crucial. Intervention methods to improve fetal circulation could provide the fetus with opportunities to rebuild its circulation, and to protect the heart, with better prognosis for the pregnancy.
  4. Impaired brain metabolism and microstructures could progress to neurodevelopmental delay after birth.
  5. Improved oxygen supply during fetal life, once critical CHD is diagnosed, might protect the developing brain and promote better neurodevelopmental outcomes.

Oxygen supply to the fetal cerebral circulation in hypoplastic left heart syndrome: a simulation study based on the theoretical models of fetal circulation.

Sakazaki S, Masutani S, Sugimoto M, Tamura M, Kuwata S, Kurishima C, Saiki H, Iwamoto Y, Ishido H, Senzaki H – Pediatric Cardiology 36: 677-684, 2015

Take Home Points:

  1. This is a fascinating simulation study on the circulation in fetuses with hypoplastic left heart syndrome, tricuspid atresia and d-transposition of the great arteries.
  2. Mathematical modeling was based on studies by Rudolph et al.
  3. According to this mathematical modeling the cerebral oxygen saturation is dramatically reduced in the heart lesions studied.
  4. Normal fetal cerebral blood oxygen saturation is estimated to be about 75%. Comparatively the fetal cerebral blood oxygen saturation in hypoplastic left heart syndrome and tricuspid atresia is estimated to be about 50%. The estimated cerebral blood oxygen saturation in d-transposition of the great arteries is lowest at 43%.
  5. These findings are interesting and in the future, studies similar to this one may shed light our understanding of CHD and neurodevelopment.

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 – Heart and Brain Research Group – Journal of Pediatrics 167; 1259-1263; 2015

Take Home Points:

  1. This study shows that infants with severe CHD without overt brain lesions have smaller global brain volumes on preoperative MRI compared with control.
  2. These findings confirm the previous reports of brain abnormalities in neonates with CHD before surgery, indicating fetal developmental and maturation abnormalities in brains of CHD infants.
  3. The effects on brain development in CHD are not focal but involve all regions of the brain.
  4. Apart from perioperative insults, the high prevalence of preoperative brain abnormalities in infants with complex CHD may be responsible for higher prevalence of cognitive impairment, motor deficits, difficulties with daily living skills, communication, and adaptive behavior in survivors of repaired CHD. Neurodevelopmental follow-up and assessment is critical in complex CHD infants.

Fetal MRI Detects Early Alterations of Brain Development in Tetralogy of Fallot.

Schellen C, Ernst S, Gruber GM, Miczoch E, Weber M, Brugger PC, Ulm B, Langs G, Salzer-Muhar U, Prayer D, Kasprian G – American Journal of Obstetrics and Gynecology 213; 2015

Take Home Points:

  1. This study from Vienna, Austria evaluated the fetal brain MRIs at a median of 25 weeks gestation in 24 fetuses with a prenatal diagnosis of tetralogy of Fallot (TOF) compared to age-matched control fetuses (n=24).
  2. Fetal MRI demonstrated significantly decreased gray matter volumes, subcortical brain volumes and total brain volumes in fetuses with (TOF) compared to the control fetuses.
  3. This fetal MRI study demonstrates early changes in the fetal brain with TOF. These finding are consistent with the hypothesis that neurodevelopmental deficits in children with congenital heart disease (CHD) are at least in part secondary to differences in fetal brain development.

Reduced Fetal Cerebral Oxygen Consumption is Associated with Smaller Brain Size in Fetuses with Congenital Heart Disease.

Sun L, Macgowan CK, Sled JG, Yoo SJ, Manlhiot C, Porayette P, Grosse-Wortmsnn L, Jaeggi E, McCrindle BW, Kingdom J, Hickey E, Miller S, Seed M – Circulation 131; 1313-1323; 2015

Take Home Points:

  1. MRI studies were conducted on 30 late gestation fetuses with CHD and 30 normal controls.
  2. Fetal brain size correlated with ascending aortic oxygen saturation and cerebral oxygen consumption.
  3. The study provides strong evidence for impaired fetal brain growth in CHDs with reduced cerebral oxygenation and raises the question of whether maternal oxygen therapy might mitigate this risk.

Severity of Fetal Brain Abnormalities in Congenital Heart Disease in Relation to the Main Expected Pattern of in Utero Brain Blood Supply.

Masoller N, Sanz-Cortes M, Crispi F, Gomez O, Bennasar M, Egana-Ugrinovic G, Bargallo N, Martinez JM, Gratacos E – Fetal Diagnosis and Therapeutics 2015

Take Home Points:

  1. This study demonstrates there are significant differences in the fetal brain at near term gestation in fetuses with CHD.
  2. Fetuses with expected severe reduction in oxygenated brain blood supply had the most significant differences.



Supporting development in children with congenital heart disease.

Brosig C, Butcher J, Ilardi DL, Sananes R, Sanz JH, Sood E, Struemph K, Hare J – Circulation 130; 175-176; 2014

Take Home Points:

This Cardiology Patient Page provides a concise overview of developmental and learning difficulties in children with high risk congenital heart disease for parents and families. This review addresses common questions regarding why patients with CHD are at higher risk for developmental delay, how to identify them and the available resources for evaluation and treatment of neurodevelopmental abnormalities.

Executive Function in Children and Adolescents with Critical Cyanotic Congenital Heart Disease.

Cassidy AR, White MT, DeMaso DR, Newburger JW, Bellinger DC – J. Int. Neuropsychol. Soc. 21; 34/49; 2015

Take Home Points:

  1. This is a compilation of the results of extensive neuropsychological evaluations performed as part of (1) the Boston Circulatory Arrest Study of children/adolescents with TGA (Bellinger et al., 2011); (2) a study of children/adolescents with TOF (Bellinger et al., 2014a); and (3) a study of children/adolescents with single-ventricle cardiac anatomy who underwent the Fontan operation (SVF; Bellinger et al., 2014b).
  2. Results indicated that executive function impairment was nearly twice as high for CHD groups (75-81%) compared to controls.
  3. The greater severity of CHD the greater impairments in executive function.

Neurodevelopmental outcomes after cardiac surgery in infancy.

Gaynor JW, Stopp C, Wypij D, Andropoulos DB, Attallah J, Atz AM, Beca J, Donofrio MT, Duncan K, Ghanayem NS, Goldberg CS, Hovels-Gurich H, Ichida F, Jacobs JP, Justo R, Latal B, Li JS, Mahle WT, McQuillen PS, Menon SC, Pemberton VL, Pike NA, Pizarro C, Shekerdemian LS, Synnes A, Williams I, Bellinger DC, Newburger JW – International Cardiac Collaborative on Neurodevelopment Investigators – Pediatrics 135; 816-825; 2015

Take Home Points:

  1. Toddlers (BSID-II testing performed at about 15 months of age) who have had cardiac surgery demonstrate decreases in psychomotor and mental development compared to normal.
  2. Risk factors of low birth weight and presence of genetic/extracardiac anomaly were associated with lower psychomotor and mental development.
  3. There was small improvement in PDI and MDI scores over time when adjusting for risk factors. However, as more high risk infants with CHD are undergoing cardiac surgery the need for development and educational resources is going to be needed.

Risk Factors for Abnormal Developmental Trajectories in Young Children with Congenital Heart Disease.

Mussatto KA, Hoffman R, Hoffman G, Tweddell JS, Bear L, Cao Y, Tanem J, Brosig C – Circulation 132; 755-761; 2015

Take Home Points:

  1. Over half of these patients had normal development in all domains.
  2. However, over 1 in 5 (21%) had delays in multiple domains.
  3. Tube feeding was associated with a substantial increase of delays across all domains.
  4. Public or no insurance was a significant predictor for delays in the cognitive domain.

Neuropsychological performance of school-aged children after staged surgical palliation of hypoplastic left heart syndrome.

Bergemann A, Hansen JH, Rotermann I, Voges I, Scheewe J, Otto-Morris C, Geiger F, Kramer HH – European Journal of Cardiothoracic Surgery 47; 803-811; 2015

Take Home Points:

  1. Patients with HLHS who have had a Norwood procedure have an average non-verbal IQ, but still score below controls in this study.
  2. Additionally, patients with HLHS have deficits specifically in verbal and visual long-term memory, executive function and processing speed.
  3. These findings closely correlate with previously published studies.

On behalf of the CHiP Network, thank you for reading!


Gary Webb, MD CHiP Network

Congenital Heart Journal Watch Editorial Board

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