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Abnormal fetal cerebral and vascular development in hypoplastic left heart syndrome
Caroline Kinnear1, Maruti Haranal2, Patrick Shannon3
1Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.
Insights
Fetuses with hypoplastic left heart syndrome (HLHS) show impaired brain growth and vascular development early in gestation. These findings suggest early vascular issues contribute to structural brain abnormalities in HLHS.
Area of Science:
- Fetal Medicine
- Developmental Biology
- Cardiovascular Research
Background:
- Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect.
- Understanding fetal brain development in HLHS is crucial for early intervention.
Purpose of the Study:
- To evaluate cerebral and vascular development in fetuses diagnosed with hypoplastic left heart syndrome (HLHS).
- To investigate potential links between vascular abnormalities and brain development in HLHS fetuses.
Main Methods:
- Study included 27 midgestation fetuses with HLHS who underwent pregnancy termination.
- Fetal echocardiography assessed aortic size and blood flow.
- Immunohistochemical staining analyzed brain sections from HLHS and control fetuses.
Main Results:
- HLHS fetuses exhibited lower head circumference z-scores.
- Cerebrovascular resistance was inversely correlated with ascending aortic size.
- Reduced capillary density, larger capillaries, and lower expression of neuronal and oligodendrocyte markers were observed in HLHS brains.
Conclusions:
- Fetal HLHS is associated with early-onset cerebral growth impairment and structural brain abnormalities.
- Abnormalities in vascular flow and differentiation of neuronal and oligodendrocyte precursors are identified.
- These findings highlight the potential role of early vascular dysfunction in the pathogenesis of brain abnormalities in HLHS.
Objective:
To assess the cerebral and vascular development in fetuses with hypoplastic left heart syndrome (HLHS).
Methods:
Pregnant women carrying fetuses diagnosed with HLHS who decided to interrupt their pregnancies were included in our study. Aortic size and blood flow were assessed based from fetal echocardiography. Immunohistochemical staining was performed in brain sections obtained from pathology in fetuses with HLHS and control fetuses without heart disease.
Results:
Twenty-seven midgestation fetal HLHS were included (gestational age, 23.3 ± 3.4 weeks). Head circumference z scores were lower in HLHS fetuses. Middle cerebral artery pulsatility index, a measure of cerebrovascular resistance, was inversely correlated with the ascending aortic z score (P < 0.05). Fetuses with HLHS had lower capillary density in the germinal matrix and their capillaries were larger compared with control fetuses with (P < 0.05). The expression of neuronal differentiation marker, FGFR1, and oligodendrocyte precursor, O4, were lower in HLHS brains compared with controls (P < 0.05).
Conclusion:
Our study identified abnormalities of vascular flow and structural brain abnormalities in fetal HLHS associated with impaired neuronal and oligodendrocyte differentiation, as well as cerebral growth impairment, early in gestation. These findings may be related in part to early vascular abnormalities.
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