Risk Factors for Perioperative Brain Lesions in Infants With Congenital Heart Disease: A European Collaboration

Abstract

Background: Infants with congenital heart disease are at risk of brain injury and impaired neurodevelopment. The aim was to investigate risk factors for perioperative brain lesions in infants with congenital heart disease. Methods: Infants with transposition of the great arteries, single ventricle physiology, and left ventricular outflow tract and/or aortic arch obstruction undergoing cardiac surgery <6 weeks after birth from 3 European cohorts (Utrecht, Zurich, and London) were combined. Brain lesions were scored on preoperative (transposition of the great arteries N=104; single ventricle physiology N=35; and left ventricular outflow tract and/or aortic arch obstruction N=41) and postoperative (transposition of the great arteries N=88; single ventricle physiology N=28; and left ventricular outflow tract and/or aortic arch obstruction N=30) magnetic resonance imaging for risk factor analysis of arterial ischemic stroke, cerebral sinus venous thrombosis, and white matter injury. Results: Preoperatively, induced vaginal delivery (odds ratio [OR], 2.23 [95% CI, 1.06–4.70]) was associated with white matter injury and balloon atrial septostomy increased the risk of white matter injury (OR, 2.51 [95% CI, 1.23–5.20]) and arterial ischemic stroke (OR, 4.49 [95% CI, 1.20–21.49]). Postoperatively, younger postnatal age at surgery (OR, 1.18 [95% CI, 1.05–1.33]) and selective cerebral perfusion, particularly at ≤20 °C (OR, 13.46 [95% CI, 3.58–67.10]), were associated with new arterial ischemic stroke. Single ventricle physiology was associated with new white matter injury (OR, 2.88 [95% CI, 1.20–6.95]) and transposition of the great arteries with new cerebral sinus venous thrombosis (OR, 13.47 [95% CI, 2.28–95.66]). Delayed sternal closure (OR, 3.47 [95% CI, 1.08–13.06]) and lower intraoperative temperatures (OR, 1.22 [95% CI, 1.07–1.36]) also increased the risk of new cerebral sinus venous thrombosis. Conclusions: Delivery planning and surgery timing may be modifiable risk factors that allow personalized treatment to minimize the risk of perioperative brain injury in severe congenital heart disease. Further research is needed to optimize cerebral perfusion techniques for neonatal surgery and to confirm the relationship between cerebral sinus venous thrombosis and perioperative risk factors.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease

“…Presurgical brain injury is more likely to result from postnatal events that lead to acute hemodynamic instability, such as the delivery process or urgent cardiac interventions. 3 Comparable to our results, Schlatterer et al did not find significant correlations between abnormal placentation and brain injury, but did observe a statistical trend toward more severe brain lesions in cases with placental abnormalities. 19 Although placental pathology may not directly cause postnatal brain injury, it could have an indirect effect, since reduced volumetric growth has been associated with increased susceptibility to postnatal brain injury.…”

“… 1 Nevertheless, these children remain at risk for neurodevelopmental sequelae, such as cognitive, motor, and behavioral problems, with reported incidence rates ranging from 20% to 60%. 2 Although these neurologic abnormalities have predominantly been attributed to cerebral vulnerability in the critical neonatal period surrounding cardiac surgery, 3 , 4 there is growing evidence that brain aberrations already develop in utero. Multiple fetal imaging studies have shown disrupted brain development in fetuses with CHD.…”

High resolution and contrast 7 tesla MR brain imaging of the neonate

“…Furthermore, it is increasingly appreciated that adverse neurocognitive outcomes following preterm birth are related to lifelong alterations in cortical development, thalamic growth and connectivity ( 37 ). Infants with congenital cardiac disease are at high risk of peri-operative hemorrhage or ischemic injury, and often have chronically reduced cerebral oxygenation ( 38 ). These factors have also been found to result in profound life-long effects on cortical maturation which are similarly associated with adverse neurodevelopmental outcomes ( 39 ).…”

Exploration of the potential of high resolution and contrast 7 Tesla MR brain imaging in neonates

“…Furthermore, it is increasingly appreciated that adverse neurocognitive outcomes following preterm birth are related to lifelong alterations in cortical development, thalamic growth and connectivity 36 . Infants with congenital cardiac disease are at high risk of peri-operative hemorrhage or ischemic injury, and often have chronically reduced cerebral oxygenation 37 . These factors have also been found to result in profound life-long effects on cortical maturation which are similarly associated with adverse neurodevelopmental outcomes 38 .…”