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Prevalence of Ischemic Brain Injury in Neonates With Congenital Heart Disease: A Systematic Review and Meta-Analysis
Caroline Kim1, Devin Chetan2, Vanna Kazazian3
1Department of Pediatrics, University of British Columbia and BC Children's Hospital Research Institute, Vancouver, Canada.
Insights
Infants with critical congenital heart disease (CHD) have a high prevalence of ischemic brain injury, affecting over 68%. Early identification is crucial for neurodevelopmental outcomes and interventions.
Area of Science:
- Neonatal Neurology
- Pediatric Cardiology
- Neurodevelopmental Pediatrics
Background:
- Infants with critical congenital heart disease (CHD) face elevated risks of brain injury and neurodevelopmental impairments.
- Existing studies report variable rates of ischemic brain injury in this vulnerable population.
Purpose of the Study:
- To systematically review and meta-analyze the prevalence of ischemic brain injury in neonates with critical CHD.
- To identify associated risk factors for brain injury in these infants.
Main Methods:
- Systematic review and meta-analysis of original research studies published up to 2024.
- Inclusion of studies reporting ischemic brain injury prevalence in neonates with critical CHD; exclusion of case reports.
- Assessment of bias using Newcastle-Ottawa Scale and revised Cochrane risk-of-bias tool; pooled prevalence calculated using random-effects models.
Main Results:
- A pooled cumulative prevalence of ischemic brain injury was found to be 68.5% in neonates with critical CHD.
- Preoperative ischemic brain injury prevalence was 34.7%, while new postoperative ischemic brain injury was 46.5%.
- Age at surgery and proportion of female sex were associated with white matter injury and arterial ischemic stroke, respectively.
Conclusions:
- Ischemic brain injury is highly prevalent in neonates with critical CHD, varying by injury type and timing.
- Identifying these injuries is vital for family counseling on neurodevelopmental outcomes and initiating early surveillance.
- Further research is needed to identify modifiable risk factors and neuroprotective strategies due to literature heterogeneity.
Background And Objectives:
Infants with critical congenital heart disease (CHD) are at increased risk of brain injury and neurodevelopmental impairments, with variable rates of ischemic brain injury reported across studies. In this systematic review and meta-analysis, we aimed to understand the overall prevalence of ischemic brain injury and associated risk factors in infants with critical CHD.
Methods:
A systematic review and meta-analysis was performed using a prespecified protocol registered on PROSPERO (CRD42021268352). Primary, original research in English reporting the prevalence of ischemic brain injury in neonates with critical CHD was included. Case reports and series were excluded. The search was conducted based on all article titles and abstracts published in MEDLINE, Embase, and Cochrane from inception to 2024. The Newcastle-Ottawa Scale for Cohort Studies and the revised Cochrane risk-of-bias tool for randomized trials were used to assess risk of bias. Random-effects restricted maximum likelihood models were used to calculate pooled prevalence rates. Funnel plots and Egger tests were used to assess publication bias. We explored associations with year of study, age at surgery, and female sex proportion using meta-regression analyses.
Results:
We identified 31 studies that reported the prevalence of ischemic brain injury in neonates with CHD. The pooled cumulative prevalence of ischemic brain injury among neonates with CHD was 68.5% (95% CI 62.7%-73.8%), with low between-study heterogeneity (I2 = 3.0%, Qp value = 0.4). The pooled cumulative prevalence of preoperative ischemic brain injury was 34.7% (95% CI 28.4%-41.5%), with moderate between-study heterogeneity (I2 = 43.4%, Qp value = 0.05), and that of new postoperative ischemic brain injury was 46.5% (95% CI 34.8%-58.5%), with substantial between-study heterogeneity (I2 = 69.1%, Qp value = 0.004). Age at surgery and female sex proportion were associated with cumulative white matter injury and preoperative arterial ischemic stroke, respectively.
Discussion:
The prevalence of ischemic brain injury in neonates with CHD is high and depends on brain injury type and timing. Identifying ischemic injuries in this population is important for counseling families about expected neurodevelopmental outcomes and beginning early neurodevelopmental surveillance and interventions. Significant heterogeneity exists in the literature; to improve outcomes, further research is warranted to determine modifiable risk factors and neuroprotective strategies.
