White Matter Injury and the Inflammatory Response Following Neonatal Cardiac Surgery

Abstract

White matter injury (WMI) is a known complication following neonatal heart surgery in term infants. In preterm infants, WMI has been associated with the degree of systemic inflammation. It is not known whether inflammation is an important mechanism of WMI as documented by magnetic resonance imaging (MRI) following neonatal heart surgery with cardiopulmonary bypass. Term neonates with congenital heart disease were enrolled in a prospective study with postoperative MRI. White matter injury was recorded by the number of T1 hyperintense foci with >5 foci consistent with significant WMI. Eleven candidate cytokine markers (INF-gamma, TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-13) were assayed preoperatively and daily for 5 days following surgery. Multiple clinical factors were recorded and correlated with WMI. Ninety-two subjects were enrolled in the study. The median age at surgery was 5 days (interquartile range 4-7 days). Compared with the presurgery level, there were statistically significant increases (p < 0.005) for 8 out of 11 inflammatory markers. In all, 64 postoperative MRIs were performed. No significant correlation was detected between WMI and clinical variables or inflammatory markers assessed immediately postoperative and on postoperative days 1 and 3, with exception of IL-1 beta on postoperative day 1. WMI correlates poorly with the systemic inflammatory response after congenital heart surgery and a number of herein measured clinical factors. WMI following neonatal heart surgery is a complex, still incompletely understood phenomenon that warrants continued investigation.

Neuroimaging findings in newborns with congenital heart disease prior to surgery: an observational study

“…The rate of WMI in infants with TGA in this study is consistent with other cohorts, which range from 14% to 38% 25 36–38 42 43 47–49. The incidence of arterial infarcts in infants with TGA has been reported between 5% and 29%,7 25 36 43 49–51 with our cohort at the lower end of this range.…”

Neurodevelopmental Abnormalities and Congenital Heart Disease

“…Infants born with complex CHD often require surgical interventions using CPB which can elicit an inflammatory response due to blood contact with foreign surfaces. Significant increases in the levels of inflammatory cytokines (8 out of 11) were recently reported following CPB surgery in CHD neonates; however, there was a weak correlation between WM injury determined by conventional MRI and inflammatory markers with IL-1β on postoperative day 1 86, 87 .…”

Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease

“…White matter injury (WMI) is described in full‐term neonates with CHD with remarkably high incidence . White matter lesions are characterized as hypo‐ and hyper‐intense on T2‐ and T1‐weighted imaging respectively, and scoring systems differ between research groups .…”