Neonatal Cardiac Disease: The Interplay between Heart and Brain

Abstract

Nowadays, nearly 90% of neonates with severe congenital heart disease (CHD) survive into adulthood. However, neonates with CHD are at increased risk of long-term neurodevelopmental sequelae, including motor delay (30-60%), language disorders (20-30%), behavioural problems (20-40%), and learning difficulties (30-50%), presumably by delayed brain development and brain injury. Therefore, the focus of research is shifting away from survival to improvement of outcomes. Intrauterine brain development is delayed in CHD, most pronounced in cortical growth, especially in neonates with transposition of the great arteries (TGA) and single ventricle physiology (SVP). A broad spectrum of preoperative and postoperative brain MRI findings is observed in neonates with severe CHD undergoing heart surgery including ischemic, haemorrhagic, and thrombotic lesions. We developed a uniform European description of perioperative brain MRI findings to accurately characterize brain lesions, for enabling future studies to identify risk factors, predict outcomes, and evaluate interventions in infants with severe CHD. Induced vaginal delivery and balloon atrial septostomy are associated with increased risk of preoperative ischemic brain lesions. Neonates with SVP, younger gestational age at birth, younger postnatal age at surgery, and selective cerebral perfusion (particularly combined with deep hypothermia) are at higher risk for new postoperative ischemic brain lesions. TGA, lower intraoperative temperature, and delayed sternal closure are risk factors for new postoperative cerebral sinovenous thrombosis. Delayed neonatal brain development and brain injury are related to less favourable early motor outcomes in infants with severe CHD. Allopurinol seems promising for a future trial, given the early neuroprotective effects, to limit hypoxic-ischemic brain injury and improve neurodevelopmental outcome in neonates with severe CHD requiring cardiac surgery with cardiopulmonary bypass. To investigate whether allopurinol administered early postnatally and perioperatively reduces brain injury and improves cardiac function and neurodevelopmental outcome, the ‘CeRebrUm and CardIac protection with ALlopurinol in neonates with severe congenital heart disease requiring cardiac surgery with cardiopulmonary bypass (CRUCIAL)’ was developed, a phase III, randomized, double blinded, placebo-controlled, Dutch multicentre trial. Primary coronary stent implantation is a feasible bridging therapy to surgery in very low birth weight infants with critical aortic coarctation.

Nowadays, an aetiology of CH can be identified in most infants. Hyperinsulinism is associated with CH in a broad range of hyperinsulinemic diseases, including maternal diabetes, congenital hyperinsulinism, insulin resistance syndromes, and hyperinsulinism-associated syndromes. The development of CH in hyperinsulinemic diseases is mainly characterized by focal hypertrophy of the interventricular septum on echocardiography. Prognosis is more favourable in CH associated with hyperinsulinism. Making the correct underlying diagnosis of CH is important for both prognosis and treatment.