Fetal brain issues in congenital heart disease

Abstract

Following the improvements in the clinical management of patients with congenital heart disease (CHD) and their increased survival, neurodevelopmental outcome has become an emerging priority in pediatric cardiology. Large-scale efforts have been made to protect the brain during the postnatal, surgical, and postoperative period; however, the presence of brain immaturity and injury at birth suggests in utero and peripartum disturbances. Over the past decade, there has been considerable interest and investigations on fetal brain growth in the setting of CHD. Advancements in fetal brain imaging have identified abnormal brain development in fetuses with CHD from the macrostructural (brain volumes and cortical folding) down to the microstructural (biochemistry and water diffusivity) scale, with more severe forms of CHD showing worse disturbances and brain abnormalities starting as early as the first trimester. Anomalies in common genetic developmental pathways and diminished cerebral substrate delivery secondary to altered cardiovascular physiology are the forefront hypotheses, but other factors such as impaired placental function and maternal psychological stress have surfaced as important contributors to fetal brain immaturity in CHD.The characterization and timing of fetal brain disturbances and their associated mechanisms are important steps for determining preventative prenatal interventions, which may provide a stronger foundation for the developing brain during childhood.

Fetal neurosonography and infant neurobehavior following conception by assisted reproductive technology with fresh or frozen embryo transfer

“…Changes in cortical development have been described in fetuses with growth restriction (FGR), congenital heart defects (CHD) and non-severe ventriculomegaly. Whereas FGR, with or without pre-eclampsia, has been associated with only reduced Sylvian fissure depth 25,30,31 , fetuses with CHD 32 or isolated ventriculomegaly 24,33 have been reported to experience a widespread suboptimal cortical folding process, with shallower sulci depths and delayed operculization, similar to that observed in our ART population.…”

Harnessing the Power of Stem Cell Models to Study Shared Genetic Variants in Congenital Heart Diseases and Neurodevelopmental Disorders

“…While traditionally intraoperative factors have been regarded as the major contributing factor to NDD in CHD, recent research has suggested an opposite direction that preoperative and innate patient factors are playing more important roles [2]. This is also in accordance with the findings that in CHD patients, changes in fetal brain size and abnormalities in brain structure have been detected as early as the second trimester [4]. Overall, this suggests that neurodevelopment is disturbed in CHD but the underlying mechanisms are less understood.…”

A diffusion MRI study of brain white matter microstructure in adolescents and adults with a Fontan circulation: Investigating associations with resting and peak exercise oxygen saturations and cognition

“…Reduced exercise tolerance is also a concern and may have important functional implications ( Tran et al, 2022 ). Chronic hypoxemia is associated with long-term morbidity and late mortality, even in cases of mild desaturation ( Schafstedde et al, 2021 , Egbe et al, 2017 , Zentner et al, 2020 ), and may be an important predisposing factor for altered cerebral development, white matter (WM) injury, and subsequent cognitive functioning ( Owen et al, 2011 , Morton et al, 2017 , Limperopoulos et al, 2010 , Sun et al, 2015 , Claessens et al, 2018 , Spaeder et al, 2017 , Claessens et al, 2019 , Rajagopalan et al, 2018 , Lee et al, 2021 , Sadhwani et al, 2022 ). Significant reductions in global brain volume and subcortical gray matter (GM) volume were associated with lower SaO 2 in our adolescent and adult Fontan cohort ( Verrall et al, 2021 ), consistent with our earlier findings from adults with other forms of cyanotic CHD ( Cordina et al, 2014 ).…”