Fetal Brain Abnormalities in Trisomy 21 and Associated Neurodevelopmental Outcome: Key Factors to Identify Differences in Neurodevelopmental Outcome?

OBJECTIVE: Trisomy 21 (T21) is associated with various neurological impairments. However, the mechanisms of fetal brain development in T21 and their impact on neurodevelopmental outcomes remain unclear, limiting prenatal counseling. Therefore, this study aims to assess neuropathological changes in fetuses with T21 and the associated neurodevelopmental outcome. METHOD: This was a case-control study comparing brain patterns in neurosonography and MRI of fetuses with T21 to healthy controls. Additionally, neurodevelopmental outcome was assessed prospectively. Thereby, an outcome score was calculated to identify brain patterns linked to unfavorable neurodevelopmental outcomes. RESULTS: 108 fetuses were included consisting of 54 fetuses with T21 and 54 controls. In the study group, significantly more fetal brain abnormalities were found compared to the control group (p < 0.001). Brain abnormalities in T21 most commonly included ventriculomegaly (24.1%), cerebellar hypoplasia (22.2%) and widening of subarachnoid fluid spaces (20.4%). Although the neurodevelopmental score showed no significant differences based on the presence of brain abnormalities, fetuses with widened subarachnoid fluid spaces or cerebellar hypoplasia were solely associated with an unfavorable outcome score. CONCLUSION: Fetuses with T21 show significantly more brain abnormalities compared with healthy controls, which should be considered for prenatal counseling. Some specific brain abnormalities were demonstrated only in the group with poorer neurodevelopmental outcomes, such as cerebellar hypoplasia and widened subarachnoid fluid spaces. However, the exploratory nature of the analysis must be considered, and additional studies are highly needed.