PROJECT SUMMARY/ABSTRACT
Congenital heart disease is the most common birth defect, affecting 0.5-2% of all live births. As medical and
surgical advances have dramatically increased survival, the burgeoning population of children and adults with
congenital heart disease has exposed a high prevalence of neurodevelopmental disabilities in survivors. By
adolescence, more than 2 out of every 3 children with critical congenital heart disease experience deficits
requiring developmental/special education services. As these children reach adulthood, their disabilities may
limit educational opportunities, employment, and quality of life.
Abnormal fetal brain development may contribute to neurodevelopmental disability in patients with congenital
heart disease. Neonates with congenital heart disease have abnormal brain structure before surgery.
Neurobiological processes that lay the foundation for long-term structural brain organization begin in utero.
Components of fetal brain critical for this process, in particular neural progenitor cells, premyelinating
oligodendrocytes, and subplate neurons, are sensitive to hypoxia-ischemia, rendering this system vulnerable to
prenatal circulatory disturbances. The impact of abnormal fetal brain development on long-term brain structure
and function in congenital heart disease is unknown. To date, there are no congenital heart disease cohorts
that have been studied in both the fetal period and later in childhood when these deficits are typically detected.
This proposal will leverage an existing fetal MRI cohort, including children both with and without congenital
heart disease, to acquire long-term neuroimaging and neurodevelopmental data at 7 years of age, thereby
determining the fetal contribution to long-term outcome. Specifically, the proposed study will investigate 1) the
association between fetal brain structure and school-age structural brain connectivity; 2) the relationship
between fetal brain structure and school-age neurodevelopmental functioning; and 3) the potential for a clinical
risk stratification tool harnessing measures available in utero to predict school-age neurodevelopmental
outcome. The overarching hypothesis is that abnormal fetal brain structure is associated with long-term
differences in structural brain connectivity and neurodevelopmental functioning in congenital heart disease.
This project will support the development of clinical risk stratification and advance the development of
interventions designed to protect the brain in children with congenital heart disease.
