# Genetic and  hemodynamic effects on prenatal cortical development in congenital heart disease

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $550,604

## Abstract

PROJECT SUMMARY/ABSTRACT
Congenital heart disease (CHD) is one of the most common congenital disorders, affecting about 1% of all live
births. More than half of children with moderate or severe CHD have neurodevelopmental disabilities (NDD)
that persist into later life. Quantitative methods that can objectively identify subjects at high risk for NDD as
early as possible are needed to allow for characterization of the mechanisms underlying NDD and monitor the
success of potential therapeutic interventions. Brain magnetic resonance imaging (MRI) studies provide
evidence for a prenatal origin of NDD by detecting reduced global brain volumes and gyrification in fetuses with
CHD. However, these whole-brain measures do not provide insight into regional brain vulnerabilities or second
trimester differences in brain development. In addition, no studies have yet explored the potential role of
genetic variants and attempted to disentangle the relative contributions of genetic and hemodynamic factors on
prenatal brain development in CHD. Since patients with single-ventricle (SV) CHD suffer high rates of NDD
and show both severe in utero reduction in oxygenated cerebral blood supply and frequent damaging genetic
variants, fetal SV CHD cohort is an ideal group in which to explore markers of altered early brain development
influenced by genetic and/or cerebral hemodynamic factors. This study will examine sulcal patterns and
regional cortical growth (thickness and surface area) to indicate the effects of genetic variants and altered
cerebral hemodynamics respectively using a large dataset of retrospective and prospective longitudinal MRIs
from the second trimester to birth with three time points in 175 SV CHD and 260 typically developing (TD)
subjects. Sulcal pattern development will be compared between SV CHD and TD subjects and correlated with
rare damaging variants in high heart expression (HHE) genes and presence of neuroprotective APOE allele in
SV CHD. We will also develop surface-based regional analysis of fetal cortical thickness and surface area.
Regional cortical thickness and surface area will be compared between SV CHD and TD subjects and
correlated with different types of cerebral blood flow in SV CHD. We hypothesize that sulcal pattern alterations
will be detected in SV CHD in the second trimester and more abnormal in SV CHD subjects with rare
damaging variants in HHE and/or neuroresilience APOE genes. Differences in cortical thickness and surface
area between SV CHD and TD subjects may be regionally inhomogeneous and more severe in the frontal
regions. Regional cortical growth will be more reduced in SV CHD subjects with aortic outflow obstruction and
retrograde aortic arch flow compared to the subjects with pulmonary obstruction with anterograde arch flow or
unobstructed outflow tracts. This project would allow early identification of the relative roles of altered genetics
and cerebral perfusion and lay the foundation for early selection and opt...

## Key facts

- **NIH application ID:** 10051735
- **Project number:** 1R01NS114087-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Kiho Im
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $550,604
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051735

## Citation

> US National Institutes of Health, RePORTER application 10051735, Genetic and  hemodynamic effects on prenatal cortical development in congenital heart disease (1R01NS114087-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051735. Licensed CC0.

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