Methods
This is a retrospective cohort study including all consecutive fetuses, who were diagnosed with isolated CDH at the University Hospitals Leuven, Belgium, between January 2007 and May 2019 (n=283), and in whom at least two MRI examinations were available (n=48 fetuses). Isolated CDH was defined as the presence of normal prenatal genetic testing either conventional karyotyping or comparative genomewide hybridization array analysis11 and the absence of a major structural anomaly. Fetuses with poor quality brain images due to motion artefacts were excluded (n=6). As controls, we used images from fetuses that underwent MRI imaging for an unrelated condition which was presumed not to involve with brain development, assessed between 20 and 37 weeks gestational age (GA) (n=26). The precise indications for MRI assessment are provided in table S1 and all brain examinations were reported as showing normal appearances for gestational age. We added to this control cohort additional fetal images (n=30) obtained by our collaborators from King’s College London (Robert Steiner MRI Unit in Hammersmith Hospital, London, U.K.) between November 2007 and May 2013 on healthy pregnant women whom had normal neurodevelopmental follow up .12 Selected patients were chosen to be equally distributed over the same gestational age period.