Brain injury in congenital heart disease: pathophysiology, MRI patterns, and perioperative risk factors

Congenital heart disease (CHD) affects approximately 1% of live births and remains a major cause of neonatal neurological morbidity. Despite advances in perioperative management, both pre- and postoperative brain injuries continue to occur frequently and contribute to adverse long-term neurodevelopmental outcomes. The aim of this review is to synthesize current MRI-based cohort studies to describe the prevalence and patterns of pre- and postoperative brain injury in CHD, elucidate the underlying pathophysiological mechanisms, and identify maternal-fetal, perioperative, and postoperative risk factors contributing to cerebral vulnerability. This review also aims to propose research strategies and clinical interventions that should be considered for their mitigation.

This narrative review integrates evidence from 11 prospective and retrospective cohort studies published between 2016 and 2025, encompassing more than 1500 infants with CHD, to support the objectives outlined above.

Preoperative brain injury is detected in 12-54% of neonates, most commonly manifesting as white matter injury (WMI), arterial ischemic stroke, or cerebral hemorrhage. Postoperative imaging reveals a predominance of WMI, focal infarctions, often thromboembolic in origin, microhemorrhages, and venous thrombosis. The underlying pathophysiology is multifactorial, involving chronic hypoxemia, impaired cerebral autoregulation, abnormal shunting physiology, hypoperfusion, ischemia-reperfusion, inflammation, and thromboembolism. Risk factors span the maternal-fetal environment (e.g., placental dysfunction, preeclampsia), perinatal and neonatal characteristics (male sex, prematurity, low birth weight), and procedural factors (surgical timing, cardiopulmonary bypass technique, hemodynamic instability, anticoagulation, and ECMO).

Neonates with CHD are highly vulnerable to brain injury both before and after surgery, with WMI and ischemic stroke as the most frequent patterns. Advances in blood pressure management, tailored perfusion strategies, and optimized surgical timing have reduced postoperative injury rates, yet substantial risks persist. Future directions in neuroprotection for neonates with CHD include the development of antenatal interventions, individualized hemodynamic management targets, incorporation of multimodal neuromonitoring, implementation of risk-stratified anticoagulation strategies, and establishment of long-term neurodevelopmental surveillance programs to reduce cerebral morbidity and enhance overall outcomes.

Brain damage in newborns with congenital heart disease often begins before surgery and continues at a high rate in the postoperative period. Contemporary MRI-based evidence reveals distinct patterns and timing of white matter injury, ischemia, and hemorrhage. This review synthesizes prenatal, perioperative, and postoperative mechanisms contributing to cerebral vulnerability. Findings support early risk stratification and precision neuroprotective strategies to improve long-term neurodevelopmental outcomes. This review integrates current MRI-based cohort data to clarify the mechanisms and risk factors in the prenatal, perioperative, and postoperative periods. It aims to provide the reader with an overview of all studies conducted on this topic in recent years.