Severe Congenital Heart Defects Are Associated with Global Reduction of Neonatal Brain Volumes

Rhein, Michael von; Buchmann, Andreas; Hagmann, Cornelia; Dave, Hitendu; Bernet, Vera; Scheer, Ianina; Knirsch, Walter; Latal, Beatrice; Bürki, Christoph; Prêtre, René; Kretschmar, Oliver; Kellenberger, Christian J.; Liamlahi, Rabia; Plecko, Barbara; Sennhauser, Felix H.

doi:10.1016/j.jpeds.2015.07.006

Cited by 109 publications

(116 citation statements)

References 29 publications

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“…This finding at one year of age complements p r i o r investigations that showed reduced total brain volume in fetuses, neonates, and adolescents with CHD. 17, 21, 28 Fetuses with hypoplastic left heart syndrome had smaller total brain volume than controls, most prominent in cerebral white matter and cortex. 18 Pre-operative neonates with predominantly biventricular CHD, scanned at less than two weeks of age, had global reductions in brain volume without pronounced regional differences.…”

Section: Discussionmentioning

confidence: 89%

“…18 Pre-operative neonates with predominantly biventricular CHD, scanned at less than two weeks of age, had global reductions in brain volume without pronounced regional differences. 28 Despite years of further brain growth and development, adolescents with CHD have reduced total brain volume, most prominent in cerebral white matter. 16, 21 Together with qualitative studies indicating that white matter injury is the most common neuroimaging finding in CHD, 13, 29 our data suggest that early developmental disturbances and brain injury lead to persistent reductions in total and cerebral white matter volume long after surgical repair.…”

Section: Discussionmentioning

confidence: 99%

“…Further, our finding of reduced total brain volume is consistent with data from other cohorts both younger and older than our subjects. 17, 21, 28 Fourth, given the era during which our neurodevelopmental data were collected, the BSID-II was used, and the third edition has been used in more recent cohorts. The significant findings with the CDI in contrast to the lack of correlations with BSID-II may reflect a lower sensitivity of the BSID-II in this regard.…”

Section: Discussionmentioning

confidence: 99%

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White Matter Volume Predicts Language Development in Congenital Heart Disease

Rollins

Asaro

Akhondi-Asl

et al. 2017

The Journal of Pediatrics

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Objective To determine whether brain volume is reduced at one year and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. Study design Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II (BSID-II) and the MacArthur-Bates Communicative Development Inventories (CDI) at one year. A multi-template based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the CHD group, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. Results Compared with controls, CHD infant had reductions of 54 mL in total brain (P = 0.009), 40 mL in cerebral white matter (P < 0.001), and 1.2 mL in brainstem (P = 0.003) volumes. Within the CHD group, brain volumes were not correlated with BSID-II scores but did correlate positively with CDI language development. Conclusion Infants with biventricular CHD show total brain volume reductions at one year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. Trial registration ClinicalTrials.gov: NCT00006183

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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White Matter Volume Predicts Language Development in Congenital Heart Disease

Rollins

Asaro

Akhondi-Asl

et al. 2017

The Journal of Pediatrics

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“…Brain MRI studies evaluating microstructural, macrostructural, and metabolic indicators of brain maturity in preoperative term neonates with CHD suggest dysmature/immature brain development, with a total brain maturational score equivalent to that of infants born approximately one month earlier. [17–20] Similarly, fetuses with CHD have approximately 10% smaller total brain volumes than healthy fetuses in utero , with delays in cortical development detected in fetuses with hypoplastic left heart syndrome as early as 25 weeks gestation. [21–23] Thus, pathophysiologic processes impeding structural brain development likely precede birth.…”

Section: Neurodevelopment and Chdmentioning

confidence: 99%

Genetic contribution to neurodevelopmental outcomes in congenital heart disease: are some patients predetermined to have developmental delay?

Rollins

Roberts

2017

Current Opinion in Pediatrics

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Purpose of review Neurodevelopmental impairment is common in children with moderate to severe congenital heart disease. As children live longer and healthier lives, research has focused on identifying causes of neurodevelopmental morbidity that significantly impact long-term quality of life. This review will address the role of genetic factors in predicting neurodevelopmental outcome in CHD. Recent findings A robust literature suggests that among children with various forms of congenital heart disease, those with known genetic/extracardiac anomalies are at highest risk of neurodevelopmental impairment. Advances in genetic technology have identified genetic causes of congenital heart disease in an increasing percentage of patients. Further, emerging data suggest substantial overlap between mutations in children with congenital heart disease and those that have previously been associated with neurodevelopmental disorders. Summary Innate and patient factors appear to be more important in predicting neurodevelopmental outcome than medical/surgical variables. Future research is needed to establish a broader understanding of the mutations that contribute to neurodevelopmental disorders and the variations in expressivity and penetrance.

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“…Even prior to initial surgery, which often occurs in the neonatal period, signs of brain injury and abnormal cerebral hemodynamics are apparent both in autopsy and MRI studies (10,11). Indeed, significant reduction in brain cortical volume has been observed recently in a heterogeneous group of neonates with CHD (12).…”

mentioning

confidence: 99%

Reduced cortical volume and thickness and their relationship to medical and operative features in post-Fontan children and adolescents

et al. 2017

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Background:We compared brain cortical and subcortical gray matter volumes and cortical thickness between postFontan patients and healthy controls, and examined brain anatomical associations with operative and medical history characteristics. Methods: Post-Fontan (n = 128 volumes; n = 115 thickness) and control subjects (n = 48 volumes; n = 45 thickness) underwent brain MRI at ages 10-19 y. Subcortical and cortical volumes and cortical thicknesses were measured for intergroup comparison. Associations between brain measures and clinical measures were assessed in the Fontan group. results: Widespread, significant reduction in brain volumes and thicknesses existed in the Fontan group compared to controls, spanning all brain lobes and subcortical gray matter. Fontan subjects treated with vs. without the Norwood procedure had smaller volumes in several terminal clusters, but did not differ in cortical thickness. Older age at first operation and increasing numbers of cardiac catheterizations, operative complications, and catheterization complications were associated with lower regional volumes and thicknesses. Increasing numbers of operative complications and cardiac catheterizations were associated with smaller regional volumes in the Norwood group. conclusion: The post-Fontan adolescent brain differs from the normal control brain. Some of these differences are associated with potentially modifiable clinical variables, suggesting that interventions might improve long-term neurocognitive outcome.c ongenital heart disease (CHD) is the most common congenital anomaly, with single ventricle (SV) defects occurring in nearly 10% of patients with CHD (1). Patients with SV, particularly hypoplastic left heart syndrome (HLHS), have higher mortality and morbidity than those with other types of CHD, but their survival has steadily increased for several decades (2). The Fontan procedure, as well as staged palliation

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Severe Congenital Heart Defects Are Associated with Global Reduction of Neonatal Brain Volumes

Cited by 109 publications

References 29 publications

White Matter Volume Predicts Language Development in Congenital Heart Disease

White Matter Volume Predicts Language Development in Congenital Heart Disease

Genetic contribution to neurodevelopmental outcomes in congenital heart disease: are some patients predetermined to have developmental delay?

Reduced cortical volume and thickness and their relationship to medical and operative features in post-Fontan children and adolescents

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