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A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse
Published on: December 16, 2022
Delayed cortical development in fetuses with complex congenital heart disease
C Clouchoux1, A J du Plessis, M Bouyssi-Kobar
1Diagnostic Imaging and Radiology.
Insights
Fetal brain development is impaired in fetuses with hypoplastic left heart syndrome (HLHS), a severe congenital heart defect. Delays in cortical folding occur early, preceding volumetric growth issues, indicating potential third-trimester brain growth failure.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatric Cardiology
Background:
- Neurologic impairment is a significant complication in complex congenital heart disease (CHD).
- Evidence suggests neurologic dysfunction is present in newborns with CHD before surgical intervention.
- Previous research indicated brain growth impairment in fetuses with CHD originates in utero.
Purpose of the Study:
- To characterize global and regional brain development in fetuses with hypoplastic left heart syndrome (HLHS).
- To investigate the origins of brain growth impairment in HLHS fetuses during the third trimester.
Main Methods:
- Utilized advanced magnetic resonance imaging (MRI) techniques.
- Compared in vivo brain growth in 18 fetuses with HLHS and 30 control fetuses.
- Analyzed brain development between 25.4 and 37.0 weeks of gestation.
Main Results:
- Demonstrated a progressive third-trimester decline in cortical gray and white matter volumes in HLHS fetuses.
- Observed significant delays in cortical gyrification in HLHS fetuses.
- Detected early local cortical folding delays (as early as 25 weeks) in multiple brain regions, preceding volumetric deficits.
Conclusions:
- Brain growth disturbances in HLHS fetuses originate in utero, specifically during the third trimester.
- Early cortical folding delays may serve as a marker for elevated risk of third-trimester brain growth failure in HLHS.
- Findings highlight the critical impact of HLHS on fetal brain development.
Abstract:
Neurologic impairment is a major complication of complex congenital heart disease (CHD). A growing body of evidence suggests that neurologic dysfunction may be present in a significant proportion of this high-risk population in the early newborn period prior to surgical interventions. We recently provided the first evidence that brain growth impairment in fetuses with complex CHD has its origins in utero. Here, we extend these observations by characterizing global and regional brain development in fetuses with hypoplastic left heart syndrome (HLHS), one of the most severe forms of CHD. Using advanced magnetic resonance imaging techniques, we compared in vivo brain growth in 18 fetuses with HLHS and 30 control fetuses from 25.4-37.0 weeks of gestation. Our findings demonstrate a progressive third trimester fall-off in cortical gray and white matter volumes (P < 0.001), and subcortical gray matter (P < 0.05) in fetuses with HLHS. Significant delays in cortical gyrification were also evident in HLHS fetuses (P < 0.001). In the HLHS fetus, local cortical folding delays were detected as early as 25 weeks in the frontal, parietal, calcarine, temporal, and collateral regions and appear to precede volumetric brain growth disturbances, which may be an early marker of elevated risk for third trimester brain growth failure.
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