Abstract:
Congenital heart defects (CHDs) affect up to 1% of all live births. They are responsible for neurodevelopmental delays initially attributed to brain damage resulting from heart surgery. Subsequently, a growing number of studies have reported that prenatal imaging can detect brain abnormalities, at or even before birth. However, very few neuropathological studies have been conducted to evaluate neuropathological changes in subjects with CHDs. The aim of our study was to evaluate in utero brain damage in fetuses/neonates with congenital cardiopathies.
To this end, we performed a neuropathological study in a cohort of 40 fetuses/neonates with isolated cardiopathy and evaluated the prevalence of brain changes in the second and third trimester of prenatal life according to sex and type of cardiopathy. Syndromic congenital cardiopathies were excluded because of possible other causes of brain damage. Our aims were (1) to identify vulnerable brain structures affected in utero in CHDs fetuses, (2) to evaluate the lesions and their potential impact on brain growth, (3) to improve our understanding of the pathogenesis of neurodevelopmental delay in children with congenital cardiopathy.
Our study included a quantified assessment of brain weight and histological examination of representative brain areas compared with age-matched controls. Statistical analyses showed that the mean brain weight was at or below the fifth percentile in most third-trimester subjects, compared with normal brain weight in all second-trimester subjects. Low brain weight in third-trimester subjects was also associated with frequent brain lesions. Neuropathological examination showed that some areas were selectively and significantly damaged, suggesting a particular vulnerability, especially white matter, its components and the germinal zone. No significant differences were observed between subjects with different types of cardiopathies and no correlation was found between fetal sex and the frequency of neuropathological lesions.
These observations have allowed us to define the neuropathological lesions in subjects with congenital cardiopathies and their timing. They are close to those observed in premature babies, probably because they occur in the same period, the third trimester, a period of particular vulnerability of the developing brain, and may share some pathogenic mechanisms. They demonstrate the impact of congenital cardiopathies on the developing brain and correlate with imaging changes reported in the literature.
