Ninety-two newborns were enrolled (): 69 at UCSF and 23 at UBC. Of these, 62 (67%) had TGA and 30 (33%) had SVP. Cardiac surgeries performed were arterial switch in 59 newborns, Norwood procedure in 28, Blalock-Taussig shunt in four, and one ductal stent with bilateral pulmonary artery banding. Three newborns required two operations prior to their second MRI: 2 needed coarction repair before the arterial switch, and one required reexploration for bleeding. The newborns had a preoperative MRI at a median age of 5 days of life (interquartile range: 3-7). Seventy-eight newborns had a postoperative MRI at a median age of 21 days (IQR: 16-27). Fourteen newborns were not scanned postoperatively: 9 expired, 4 needed permanent pacemaker wires, and 1 family withdrew from the study after a Blalock-Taussig shunt.
Clinical description of the cohort by study centre: University of British Columbia (UBC) and University of California San Francisco (UCSF)
Preoperative Brain Injury
Brain injury was identified in 40 (43%) newborns on preoperative MRI (): stroke in 23 (), WMI in 21 () and IVH in 7. The incidence of preoperative brain injury did not differ significantly by centre (P=0.3, ). Eleven newborns had multiple lesions: 6 with stroke and WMI, 3 with stroke and IVH, and 2 with WMI and IVH. Strokes were solitary (23/23) and small (22/23) with most involving the middle cerebral artery (MCA) territory (19/23) and a minority in the posterior cerebral artery (PCA) territory (4/23). Strokes were clinically silent in all newborns. Ten newborns had solitary white matter lesions (): 5 classified as strokes (> 3mm in size) and 5 as WMI (≤3mm in size). One newborn had evidence of watershed injury following perinatal depression (delivered “flat” following shoulder dystocia, Apgar of 5 at 5 minutes, cord ph=7.02); no other newborn had a pattern of injury typical of global hypoxia-ischemia in the term newborn.(13
) Small subdural hemorrhages without mass effectwere seen in 13 newborns.
Patterns of Brain Injury: stroke and white matter injury (WMI)
Risk factors for Preoperative Brain Injury
Higher preoperative SaO2 was protective for preoperative brain injury (OR=0.96, 95%CI: 0.94-0.99, P=0.007). Balloon atrial septostomy (BAS) doubled the risk for preoperative brain injury (RR=2, 95%CI: 1.29-3.65, P=0.003) (). The risk of preoperative brain injury was not associated with the centre (P=0.3), the location (catheterization lab versus bedside) (P=0.2) nor the route of BAS (femoral versus umbilical vein) (p=0.9). When BAS and preoperative SaO2 were included in a multivariable model, BAS remained a significant risk factor for acquired brain injury (OR=3.6, 95%CI: 1.2-10.7, P=0.02) while SaO2 did not (OR=0.98, 95%CI: 0.95-1, P=0.3).
Clinical description of newborns with preoperative brain injury (N=40) relative to those without preoperative brain injury (N=52)
When examining specific brain injuries, the risk of stroke was even more strongly related to BAS (RR=4, 95%CI: 1.5-9.3, P=0.0015) and lower SaO2 (OR=0.95, 95%CI: 0.92-0.98, P=0.002). Neither the centre (P=0.3), location of the BAS procedure (P=0.3) nor the route (P=0.9) of BAS significantly impacted this risk. All 18 newborns with TGA and stroke required a BAS. Newborns with WMI were more likely to have caesarean section delivery (31% versus 10%, P=0.05) and preoperative cardiac arrest (10% versus 0%, P=0.05).
Given the difficulty coding a solitary white matter lesion as WMI or stroke, we repeated our main analyses recoding all solitary white matter lesions as strokes, and again considering them all as WMI. The relationship of BAS and SaO2 with stroke remained significant even if all the solitary white matter lesions were classified as strokes (BAS: P=0.002; SaO2: P=0.002) or WMI (BAS: P=0.015; SaO2: P= 0.005).
Progression of Brain Injury
Preoperatively identified brain injury did not progress or extended from the pre-to postoperative MRI (0/40 [95% CI: 0-7%](14
)). Progression of injury was not observed in the two newborns with pre-operative injury who did not require cardiopulmonary bypass for surgery. The median time interval between the preoperative MRI scan and cardiac surgery was 2 days (IQR: 1-5), while the one between BAS and cardiac surgery was 7 days (IQR: 5-12), and that between the pre- and postoperative MRI scan was 14 days (IQR: 9-20). The age at surgery did not significantly differ in newborns with and without preoperative brain injury (). A number of the preoperative lesions became smaller and more difficult to detect on the postoperative MRI (3/23 strokes, 3/21 WMI, and 2/7 IVH).
New Postoperative Brain Injury
New postoperative brain injury was seen in 32 newborns (40%) (): stroke in 8, WMI in 24 and IVH in 1. Strokes were solitary (8/8) and small (7/8) with 7 in the MCA territory (7/8) and one in the PCA territory. Strokes were clinically silent in all newborns. WMI was mild in 3 newborns, moderate in 9, and severe in 2. Patterns of injury suggestive of global hypoxia-ischemia were not seen. New subdural hemorrhage was seen in 12 newborns, but none showed mass effect. The incidence of new postoperative brain injury did not differ significantly by centre (P=0.8, ). Of the five newborns requiring ECLS surviving to the second MRI scan, new postoperative brain injury was seen in 2 (40%); new postoperative brain injury was seen in 29 of 68 newborns not requiring ECLS (P>0.9). Of the three newborns not requiring cardiopulmonary bypass who underwent a second MRI scan, new postoperative brain injury was seen in 1 (33%; P>0.9 relative to the remainder of the cohort). New postoperative brain injury was seen in 13/33 newborns (39%) with preoperative brain injury and in 29/44 with normal preoperative scans. Thus, the presence of preoperative brain injury was not a significant risk factor for acquiring new injury on postoperative MRI studies (RR=0.9, 95% CI: 0.53-1.56, P=0.8).