## 2 Introduction  
Congenital heart disease (CHD) affects 1% of live births each year [1; 2]. As the surgical care for CHD improves, there remains a lingering increased risk of poor neurodevelopmental outcomes for patients with CHD across the lifespan. The mechanism for neurodevelopmental abnormalities in non-syndromic CHD is unknown and is thought to be related to fetal exposure to reduced substrate delivery/hypoxia or a genetic underpinning. Genetic abnormalities are detected in approximately 50% of children with syndromic CHD and in approximately 10% of children without a recognizable clinical phenotype [3]. Significant overlap is present between deleterious de novo mutations and previously reported mutations associated with neurodevelopmental disorders [4], suggesting that genetic mutations that cause CHD may also be important in the etiology of neurodevelopmental deficits [5; 6]. Smaller brain volumes and dysmature brain structures are seen in neonates and fetuses with CHD before cardiac surgery, suggesting that prenatal and pre-operative factors, including poor substrate delivery (hypoxia/ischemia) may play an important role in altering brain development [7; 8; 9]. Preterm CHD infants also have abnormal brain development [10]. Within our current understanding of neurogenesis, there is little known about the role that deep grey and subcortical regions play in mediating poor neurodevelopmental outcomes in relation to genetic alterations. Recent animal models and correlative neuropathological studies suggest that cortical dysmaturation is linked to white matter abnormalities, including developmental vulnerability of the subplate in CHD [11; 12]. Recent neuroimaging studies have documented paralimbic-related subcortical morphological abnormalities in CHD patients across the lifespan, [13; 14; 15; 16; 17], but the relationship between paralimbic-related subcortical morphological abnormalities and clinical and neurodevelopmental outcomes in CHD is also unknown [18; 19; 20; 21]. Children with CHD are at a higher risk of developing brain dysmaturation, a generalized term encompassing abnormal and delayed development of brain macro- and microstructure [15; 22; 23; 24; 25]. CHD patients are also at risk for acquired brain injury, including infarcts and small vessel disease across their lifespans as detected by conventional neuroimaging studies. Clinical neuroimaging studies are also becoming more common to obtain in patients during the peri-operative period based on recently published guidelines. Most conventional semi-quantitative MRI scoring systems in CHD patients have exclusively focused on either acquired brain injury or cortical maturation assessment, particularly in the neonatal period [26; 27; 28; 29; 30; 31; 32; 33]. We recently developed and validated an infant semi-quantitative score that extended beyond cortical maturation and acquired brain injury to include morphological alterations in paralimbic-related subcortical structures (including cerebellum, hippocampus, olfactory bulb abnormalities), cerebrospinal fluid (CSF)-related abnormalities (including increased extra-axial CSF in frontotemporal regions), and the corpus callosum, known as a brain dysplasia score (BDS), informed by preclinical models of CHD, specifically hypoplastic left heart syndrome (HLHS). We focused our analysis on paralimbic-related subcortical structures that are known to undergo neurogenesis in early development and across the lifespan, including the olfactory bulbs, hippocampus, and cerebellum. We have recently described a similar pattern of structural subcortical dysmaturation both in human infants with CHD and genetically relevant ciliary motion dysfunction and in relation to preclinical models of CHD including hypoplastic left heart syndrome (HLHS) [34; 35; 36; 37; 38]. We have previously shown that the BDS correlates with abnormal neonatal brain white matter connectivity patterns [39] but have yet to validate this scoring system in a large dataset in relation to clinical and neurodevelopmental outcomes.