Neurodevelopmental Abnormalities and Congenital Heart Disease

Abstract

In the past two decades it has become evident that individuals born with congenital heart disease (CHD) are at risk of developing life-long neurological deficits. Multifactorial risk factors contributing to neurodevelopmental abnormalities associated with CHD have been identified; however the underlying etiologies remain largely unknown and efforts to address this issue have only recently begun. There has been a dramatic shift in focus from newly acquired brain injuries associated with corrective and palliative heart surgery to antenatal and preoperative factors governing altered brain maturation in CHD. In this review, we describe key time windows of development during which the immature brain is vulnerable to injury. Special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function. In addition, we describe current gaps in knowledge and offer perspectives about what can be done to improve our understanding of neurological deficits in CHD. Ultimately, a multidisciplinary approach will be essential in order to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD.

Microstructural Alterations and Oligodendrocyte Dysmaturation in White Matter After Cardiopulmonary Bypass in a Juvenile Porcine Model

“…Hospital mortality for neonates and infants with severe/complex congenital heart disease (CHD) has dramatically improved over the past 2 decades . However, many survivors of complex CHD repair are at significant risk for important neurodevelopmental morbidity . Within a wide range of brain regions, newly developed postoperative white matter (WM) injury is common .…”

Genome-wide Studies Reveal the Essential and Opposite Roles of ARID1A in Controlling Human Cardiogenesis and Neurogenesis from Pluripotent Stem Cells

“…Developmental heart and brain have complex interactions at multiple levels. For example, neural crest cells (NCCs), capable of differentiation into peripheral neurons and glia, migrate from the pharyngeal arch arteries (PAA) and heart outflow tract (OFT) to the primitive heart, and give rise to smooth muscle, connective tissue, and great arteries of the heart [4]. Notably, newborns with congenital heart defects exhibited a high frequency of neurodevelopmental deficits [4,5].…”

“…For example, neural crest cells (NCCs), capable of differentiation into peripheral neurons and glia, migrate from the pharyngeal arch arteries (PAA) and heart outflow tract (OFT) to the primitive heart, and give rise to smooth muscle, connective tissue, and great arteries of the heart [4]. Notably, newborns with congenital heart defects exhibited a high frequency of neurodevelopmental deficits [4,5]. Previous studies revealed that epigenetic regulatory mechanisms, such as DNA methylation [6], histone modifications [7], and chromatin remodeling [8][9][10][11], played essential roles in heart and neural development in mammals.…”

Commentary: Nitric oxide: An important contributor to neuroprotection during pediatric cardiac surgery

“…It is now clear that the etiology of neurologic deficits in children with congenital heart disease (CHD) is cumulative and multifactorial. 7 Alterations in fetal cerebral oxygen delivery cause immature and delayed brain development before birth and before surgery. Lawrence and colleagues 8 recently demonstrated with a unique ''artificial womb'' system that prenatal and preoperative chronic hypoxemia result in similar alterations in microglial morphology in fetal sheep.…”