Fetal Heart and Brain

Children with complex forms of congenital heart disease can have developmental and learning differences throughout infancy, childhood and adolescence. It is important that we identify these differences early and recommend interventions so children can thrive and reach their potential. Our study team has made several critical discoveries over the last decade including the observations that babies with severe congenital heart disease have evidence of delayed brain development and are at high risk for mild forms of brain injury which can lead to some differences in motor and cognitive outcomes. The Fetal Heart & Brain Study aims to determine whether we can predict early in fetal life which children are going to be at highest risk for these differences so that we can think of ways to intervene earlier, beginning in utero. To do this we are using novel imaging techniques including fetal brain MRI and fetal echocardiography to study the heart and brain of fetuses affected with complex forms of congenital heart disease. After birth, we continue to study the heart and brain using a combination of imaging and standardized developmental tests that are administered by specialized members of the study team as part of the CHD-MRI study.

Thanks to the advancements in technology and peri-operative care of newborns with congenital heart disease, more children are growing up and learning to live with their heart defect. Our goals are to ensure that these children have the best possible quality of life by optimizing their development and providing support where needed. The Fetal Heart & Brain Study begins that process before birth. Work from the Fetal Heart & Brain study was supported by a NIH/NINDS K23 grant (PI: Peyvandi).

Results from the Fetal Heart & Brain study include:

Cerebral oxygenation is impaired in fetuses with CHD compared with controls

This study utilized novel methodology called T2* MRI to obtain a global measurement of cerebral oxygenation in fetuses during the 3rd trimester. We observed that fetuses with both d-transposition of the great arteries and hypoplastic left heart syndrome had lower cerebral oxygenation compared with controls. This likely demonstrates differences in cerebral metabolism as well and reflects the effects of abnormal cardiovascular physiology on the developing fetal brain. Along with our collaborators we have identified a prenatal imaging tool that can provide quantitative information about the fetal brain efficiently that can be used in future neuroprotective trials.

Learn more: Fetal Cerebral Oxygenation Is Impaired in Congenital Heart Disease and Shows Variable Response to Maternal Hyperoxia

Brief administration of maternal hyperoxia leads to variable changes in cerebral oxygenation and flow patterns

Previous studies have suggested that oxygen delivery to the developing fetal brain is impaired in the context of complex CHD. This has led to the hypothesis that administration of supplemental oxygen to the fetus via maternal hyperoxia may optimize oxygen delivery and optimize brain development. As a first step we tested the response of the fetal brain (both T2* MRI and cerebral flow patterns by ultrasound) to brief administration of maternal hyperoxia. We observed significant variability depending on the underlying congenital heart defect as well as significant variability between participants. Our findings suggest that the underlying cardiovascular physiology is a critical factor in future neuroprotective trials—in other words we must conduct more multi-center studies to study homogeneous groups of patients and have adequate sample size to make meaningful discoveries!

Learn more: Fetal Cerebral Oxygenation Is Impaired in Congenital Heart Disease and Shows Variable Response to Maternal Hyperoxia, Fetal cerebrovascular response to maternal hyperoxygenation in congenital heart disease: effect of cardiac physiology

Brain immaturity predisposes neonates with CHD to white matter injury

Patients with CHD have delayed brain development and are at risk for brain injury after birth. In this longitudinal study from fetal to neonatal life, we identify an association between brain immaturity and acquired brain injury in d-Transposition of the great arteries. These findings form the premise of the TRANSIT CHD study.

Learn more: Fetal brain growth and risk of postnatal white matter injury in critical congenital heart disease

Next Steps:

Our future goals are to determine whether measurements of fetal brain development, including growth and metabolism, are associated with postnatal measures of brain health and neurodevelopmental outcomes.

Pediatric Heart and Brain Research Program

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Results from the Fetal Heart & Brain study include:

Next Steps: