Neurology. 2026 Feb 10;106(3):e214569. doi: 10.1212/WNL.0000000000214569. Epub 2026 Jan 9.
ABSTRACT
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.
PMID:41512205 | DOI:10.1212/WNL.0000000000214569