Prenatal Cardiovascular Physiology and Early Neurodevelopment in Cyanotic Congenital Heart Disease

Advancements in infant cardiovascular surgery have resulted in a significant decrease in mortality of many newborns with congenital heart disease (CHD); however, neurodevelopmental delays and disorders (NDD) are common comorbidities. Studies have demonstrated delays in brain growth and maturation begin as early as the third trimester, with correlations to early neurodevelopmental outcomes. These disturbances have been linked to disruptions in cerebral oxygenation due to the abnormal cardiac connections and obstructed blood flow that characterize CHD. Recently, our group developed an updated fetal cardiovascular magnetic resonance (CMR) approach to non-invasively assess patient-specific hemoglobin concentration, in addition to vessel blood flow and oxygen saturation to measure oxygen transport across the fetal circulation. Among fetuses with cyanotic CHD, diminished fetal combined ventricular output was associated with mortality, whereas cerebral blood flow and oxygen delivery were associated with early cognitive, language, and motor development at 18-months of age, suggesting a role for fetal CMR in early NDD risk stratification. In transposition of the great arteries, acute maternal supplemental oxygen (MSO) at 70% fraction of inspired oxygen (FiO2) was associated with an increase in fetal oxygen saturations. However, cerebral oxygen delivery did not improve likely due to a combination of direct vasoconstricting effect of higher cerebral circulatory oxygen saturations and potentially an element of steal into the pulmonary circulation. However, baseline fetal CMR was helpful in confirming severe restriction at the atrial septum in the case of an intact ventricular septum, by evidence of reversal of the expected gradient of oxygen saturations across the left and right ventricles which may help identify patients that may require fetal or urgent neonatal BAS in the delivery room. In a pilot safety and feasibility trial of a cohort of 25 fetuses with single ventricle physiology, continuous MSO at 40% FiO2 from mid-gestational diagnosis until delivery was safe and feasible. However, a secondary analysis revealed there were no significant changes in fetal cerebral oxygen delivery or improvements in early neurologic and neurodevelopmental outcomes. This thesis supports the clinical utility of fetal CMR to help identify patients at risk of adverse neonatal compromise and NDD outcomes. However, chronic MSO would not appear to represent a neuroprotective strategy in the setting of CHD.

Department dc:contributor.department

Physiology

Year dc:date.issued

2024

Author dc:creator

• Lee, Fu-Tsuen

Advisor dc:contributor.advisor

• Seed, Michael

• Cardiac Magnetic Resonance
• Clinical Trial
• Congenital Heart Disease
• Maternal Hyperoxygenation
• Neurodevelopment
• Perinatal

Statement dc:rights

• Attribution 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/140843

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/140843