Risk factors for preoperative periventricular leukomalacia in term neonates with hypoplastic left heart syndrome are patient related

Abstract

BACKGROUND Preoperative brain injury is common in neonates with complex congenital heart disease. Increasing evidence suggests a complex interaction of prenatal and postnatal risk factors for development of brain white matter injury called periventricular leukomalacia (PVL) in neonates with complex congenital heart disease. To date, there remains a limited understanding of the risk factors contributing to preoperative PVL in hypoplastic left heart syndrome (HLHS). METHODS Neonates with HLHS or HLHS variants from three prospective MRI studies (2003–2010) were selected for this cohort. A preoperative brain MRI was performed the morning of the surgery. Stepwise multilogistic regression of patient characteristics, mode of delivery (cesarean section vs. vaginal), time of diagnosis (prenatal vs. postnatal), HLHS subtypes, brain total maturation score (TMS), time to surgery, individual averaged daily preoperative blood gases and CBC values was used to determine significant associations. RESULTS A total of 57 neonates with HLHS were born at 38.7 ± 2.3 weeks, 86% (49/57) had a prenatal diagnosis with 31% (18/57) delivered by cesarean section. HLHS with aortic atresia (AA) was common in this cohort, (41/57, 71%). Preoperative PVL was identified in 19% (11/57). Male patients with aortic atresia (p=0.004) were at higher risk for PVL. Lower total brain maturation score was also identified as a strong predictor for preoperative PVL (p=0.005). CONCLUSIONS In neonates with HLHS, non-modifiable patient related factors including male gender with aortic atresia (lack of antegrade blood flow) and lower total brain maturation score placed neonates at the greatest risk for preoperative white matter injury.

Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome

“…Other patient characteristics such as gender and HLHS subtype (i.e. aortic atresia or aortic stenosis), which have previously been shown to be significant predictors of pre-operative PVL, 29 were not significant predictors of acquired post-operative injury in this cohort.…”

Association of Prenatal Diagnosis of Critical Congenital Heart Disease With Postnatal Brain Development and the Risk of Brain Injury

“…14,20,23 The mechanism of WMI is thought to be secondary to hypoxic-ischemic and inflammatory injury to susceptible immature premyelinating oligodendrocytes similar to the mechanism seen in preterm infants. 24 Indeed, brain immaturity has been reported in both fetal and neonatal imaging performed in patients with hypoplastic left heart syndrome, 17,18,25 perhaps resulting in an increased susceptibility to focal and diffuse WMI.…”

Neurological Injury and Cerebral Blood Flow in Single Ventricles Throughout Staged Surgical Reconstruction

“…Neonates and infants with congenital heart disease undergoing magnetic resonance have been found to have significant brain lesions before and after cardiac surgery, 2,7,17,18,19 the incidence increasing with brain immaturity. 20 In the case of single ventricle lesions, reasons for preoperative neurological injury may include genetic syndromes, low cardiac output, events such as cardiac arrest, fetal and neonatal ischemia as well as cyanosis causing hypoxia.…”

“…2,3,4,5,6,7 This has presumably led to the findings of poor neurodevelopmental outcome in this patient population. 8,9,10,11 The etiology of these brain lesions is multifactorial and includes genetics, cyanosis and numerous surgeries which involve cardiopulmonary bypass and deep hypothermic circulatory arrest.…”