Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease

Abstract

Objective Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region‐specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development. Methods From 2014 to 2018, we enrolled 179 pregnant women into 4 groups: “HLHS/TGA” fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA), diagnoses with lowest fetal cerebral substrate delivery; “CHD‐other,” with other CHD diagnoses; “CHD‐related,” healthy with a CHD family history; and “optimal control,” healthy without a family history. Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables. Results HLHS/TGA (n = 24), CHD‐other (50), and CHD‐related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD‐related, the HLHS/TGA group had smaller subplate (−13.3% [standard error = 4.3%], p < 0.01) and intermediate (−13.7% [4.3%], p < 0.01) zones, with a similar trend in ventricular zone (−7.1% [1.9%], p = 0.07). These volumetric reductions were associated with lower cerebral substrate delivery. Interpretation Fetuses with CHD, especially those with lowest cerebral substrate delivery, show a region‐specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation. The brains of fetuses with CHD were more similar to those of CHD‐related than optimal controls, suggesting genetic or environmental factors also contribute. ANN NEUROL 2021;89:143–157

Optimal Method for Fetal Brain Age Prediction Using Multiplanar Slices From Structural Magnetic Resonance Imaging

“…Under tight genetic control, quantitative structural brain features, including brain volume, cortical gyrification, surface area, curvature, and sulcal depth, were strongly correlated with GA and small intersubject variations in typically developing (TD) fetuses ( Rajagopalan et al, 2011 ; Clouchoux et al, 2013 , 2012 ; Hu et al, 2013 ; Wright et al, 2014 ; Namburete et al, 2015 ; Wu et al, 2015 ; Lefèvre et al, 2016 ; Andescavage et al, 2017 ). Moreover, atypical structural features have been more frequently found in fetuses with ventriculomegaly, congenital heart disease, and Down syndrome than in TD fetuses ( Clouchoux et al, 2012 ; Scott et al, 2013 ; Kyriakopoulou et al, 2014 ; Lefèvre et al, 2016 ; Jaimes et al, 2020 ; Tarui et al, 2020 ; Rollins et al, 2021 ; Yun et al, 2021 ). Therefore, prediction of fetal brain age based on structural MRI features may be useful for detecting abnormalities in brain development and the risk of adverse developmental outcomes.…”

Reference biometry of foetal brain by prenatal MRI and the distribution of measurements in foetuses with ventricular septal defect

“…The value of TCD in 56% (10/18 cases) foetuses with VSD was lower than the 3rd centile, and the rates for FOD and BPD were 33% (6/18 cases) and 22% (4/18 cases) separately. Rollins has suggested that the involvement of brain size in the foetus with hypoplastic left heart syndrome or transposition of the great arteries was in a region-specific pattern [ 31 ]. Regional involvement of the brain was also observed in foetuses with single ventricle congenital heart disease [ 32 ].…”

Fetal origin of brain dysmaturation in congenital heart disease – Challenges and opportunities for interventions

“…in the fetal MRI study of Rollins et al [9] is of importance because this region in the last 16 weeks of gestation is the site of differentiating premyelinating oligodendrocytes (pre-OLs), rapidly growing axons, and late migrating GABAergic neurons.…”

“…see earlier).The third region affected in the fetal study ofRollins et al is the ventricular-subventricular zone[9]. These germinative sites in the last 16 weeks of gestation give rise to the GABAergic neurons destined for cerebral cortex, as just described, as well as progenitor cells for pre-OLs.…”

“…However, this increased survival rate has been accompanied by a large burden of neurodevelopmental deficits. Although neurologi- Impaired fetal growth trajectories became apparent before 32 weeks' gestational age and involved the subplate zone, the intermediate ("white matter") zone, and the ganglionic eminence and subventricular zone [9]. The subplate zone is crucial for brain development via the role of subplate neurons (SPN) in development of cerebral cortex.…”