Oxygen Supply to the Fetal Cerebral Circulation in Hypoplastic Left Heart Syndrome: A Simulation Study Based on the Theoretical Models of Fetal Circulation

Abstract

Hypoxia due to congenital heart diseases (CHDs) adversely affects brain development during the fetal period. Head circumference at birth is closely associated with neuropsychiatric development, and it is considerably smaller in newborns with hypoplastic left heart syndrome (HLHS) than in normal newborns. We performed simulation studies on newborns with CHD to evaluate the cerebral circulation during the fetal period. The oxygen saturation of cerebral blood flow in newborns with CHD was simulated according to a model for normal fetal circulation in late pregnancy. We compared the oxygen saturation of cerebral blood flow between newborns with tricuspid atresia (TA; a disease showing univentricular circulation and hypoplasia of the right ventricle), those with transposition of the great arteries (TGA; a disease showing abnormal mixing of arterial and venous blood), and those with HLHS. The oxygen saturation of cerebral blood flow in newborns with normal circulation was 75.7 %, whereas it was low (49.5 %) in both newborns with HLHS and those with TA. Although the oxygen level is affected by the blood flow through the foramen ovale, the oxygen saturation in newborns with TGA was even lower (43.2 %). These data, together with previous reports, suggest that the cerebral blood flow rate is decreased in newborns with HLHS, and the main cause was strongly suspected to be retrograde cerebral perfusion through a patent ductus arteriosus. This study provides important information about the neurodevelopmental prognosis of newborns with HLHS and suggests the need to identify strategies to resolve this unfavorable cerebral circulatory state in utero.

The neurodevelopmental implications of hypoplastic left heart syndrome in the fetus

“…In hypoplastic left heart syndrome, the entire cerebral circulation is dependent on the retrograde flow from the arterial duct through the aortic isthmus, with potential restriction to blood flow to the aortic arch and head and neck vessels ( Fig 1b ). 33 Microcephaly is known to be associated with reduced cerebral blood flow before birth, 34 , 35 and has also been independently associated with a diminutive ascending aorta in hypoplastic left heart syndrome patients. 7 Cerebral autoregulatory mechanisms offer further insight: during periods of hypoxic stress, the normal fetus compensates by reducing cerebrovascular resistance to re-distribute blood flow to the upper body and brain.…”

Volumetric Brain MRI Study in Fetuses with Congenital Heart Disease

“…Another aspect of the contribution of our study is that so far, results on brain volume reduction mainly focused on HLHS and TGA. 2,6,[8][9][10]20 In our study, we demonstrated these effects in various types of CHD because our cohort comprised only 4 cases of HLHS (ϳ9%) and 9 cases of TGA (ϳ20%). Masoller et al 18 addressed this question and compared the fetal neurodevelopment between 2 groups of fetuses with CHD divided according to the expected blood supply to the brain, with group A containing only HLHS, TGA, critical aortic stenosis, and hypoplastic aortic arch.…”

Three‐Dimensional Volumetric Magnetic Resonance Imaging Detects Early Alterations of the Brain Growth in Fetuses With Congenital Heart Disease

“…12 It is generally assumed that left-sided CHD such as HLHS represents a higher risk for brain lesions and developmental delay due to the massive reduction in perfusion of placental well-oxygenated blood supply to the fetal brain. 21 However, other CHD types with prenatal brain blood supply can also be associated with prenatal neurological injury. A good example occurs in TGA, 22 where oxygen saturated blood enters the pulmonary artery to supply the lungs and lower body, while the fetal brain receives deoxygenated blood from the right ventricle.…”