Early brain magnetic resonance imaging findings and neurodevelopmental outcome in children with congenital heart disease: A systematic review

Background Brain magnetic resonance imaging (MRI) of infants with congenital heart disease (CHD) shows brain immaturity assessed via a cortical-based semi-quantitative score. Our primary aim was to develop an infant paralimbic-related subcortical-based semi-quantitative dysmaturation score, a brain dysplasia score (BDS), to detect abnormalities in CHD infants and predict clinical outcomes. Our secondary aim was to validate our BDS in a preclinical mouse model of hypoplastic left heart syndrome. Methods A paralimbic-related subcortical BDS, derived from structural MRIs of infants with CHD, was correlated with clinical risk factors, regional cerebral volumes, feeding and 18-month neurodevelopmental outcomes. The BDS was validated in a known CHD mouse model named Ohia with two disease-causing genes, Sap130 and Pchda9. To relate clinical findings, RNA-Seq was completed on Ohia animals. Findings BDS showed high incidence of paralimbic-related subcortical abnormalities (including olfactory, cerebellar, and hippocampal abnormalities) in CHD infants (n=215) compared to healthy controls (n=92). BDS correlated with reduced cortical maturation, developmental delay, poor language and feeding outcomes, and increased length of stay. Ohia animals (n=63) showed similar BDS findings, and RNA-Seq analysis showed altered neurodevelopmental and feeding pathways. Sap130 mutants correlated with a more severe BDS whereas Pcdha9 correlated with a milder phenotype. Interpretation Our BDS is sensitive to dysmaturational differences between CHD and healthy controls, and predictive of poor outcomes. A similar spectrum of paralimbic-related subcortical abnormalities exists between human and Ohia mutants suggesting a common genetic mechanistic etiology.

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Neuromonitoring modalities predicting neurological impairment in pediatric congenital heart disease: a systematic review

Van Loo,

Cools,

Dereymaeker

et al. 2024

Front. Neurol.

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The increased risk of neurodevelopmental impairment in children with congenital heart disease (CHD) has been established, but the search for targeted neurological predictors of adverse outcome is ongoing. This systematic review reports on the utility of three functional neuromonitoring modalities, Near-infrared Spectroscopy (NIRS), electroencephalography (EEG) and biochemical biomarkers, in predicting either clinical neurodevelopmental outcome or structural brain abnormalities after pediatric CHD surgery. Medline, Embase, CENTRAL, Web of Science, clinicaltrials.gov and ICTRP were systematically searched for eligible articles. Original research articles, written in English, published before November 2023 and reporting on perioperative NIRS, EEG or biomarkers and their association with clinical neurodevelopmental outcome or neuroimaging in children <17 years undergoing surgery for CHD were included. The search yielded 11,367 citations, of which 40 papers were included in the final review: sixteen articles (n = 908 cases) reported on NIRS, twelve (n = 1,163) on EEG and fifteen (n = 903) on biochemical biomarkers. Three papers reported on a combination of modalities. Median age at time of surgery was 9 (IQR 7–57) days. Postoperative MRI was performed before discharge at varying timepoints. Median age at clinical outcome assessment was 15 (IQR 12–24) months. Limited evidence supports an association of cerebral oxygen extraction, cerebral desaturation and cerebral autoregulation with outcome, but there was significant heterogeneity in results. Perioperative electroencephalographic ictal discharges and abnormal background were associated with impaired neurological outcome and abnormal neuroimaging. Numerous biochemical biomarkers have been reported but showed no consistent relationship with outcome, except for lactate, which could serve as a predictor of poor outcome. There is a need for larger homogeneous cohorts of children with CHD to determine which perioperative modalities might serve as predictors of neurodevelopmental outcome or neuroimaging abnormalities.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO, CRD42023479344

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Early brain magnetic resonance imaging findings and neurodevelopmental outcome in children with congenital heart disease: A systematic review

Cited by 4 publications

References 99 publications

School Readiness in Preschool-Age Children with Critical Congenital Heart Disease

School Readiness in Preschool-Age Children with Critical Congenital Heart Disease

Development and Validation of a Paralimbic Related Subcortical Brain Dysmaturation MRI Score in Infants with Congenital Heart Disease

Neuromonitoring modalities predicting neurological impairment in pediatric congenital heart disease: a systematic review

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