Interpretation
On postnatal imaging, Danzer et al. reported a lower total maturation
score in CDH infants after birth (6). Along the same lines, Lucignani et
al reported reduced cortical maturation in extended brain areas of CDH
newborns compared to healthy controls. 25 In earlier
studies based on prenatal images, fetuses with CDH had brain
sulcation scores, which are indicators of prenatal brain maturation,
within the normal range between 20 and 37 weeks.8, 26One study on infants who had both pre- and postnatal imaging, reported
signs of brain injury (e.g. hemorrhage, white matter injury, …)
on postnatal, but not on prenatal MRI . In that study , the injury
score correlated with the degree of pulmonary hypoplasia, evidenced by
the o/e TFLV.26 Also, there was no indication of
delayed sulcation in the prenatal period in those fetuses.
Conversely, this study demonstrates that CDH fetuses have indications of
atypical brain development, i.e. there was a significant delay at 28
weeks and 33 weeks of gestation. By 33 weeks the quantitative scores
were in the normal range. However, quantitative scoring was performed on
primary and not on secondary sulci, limiting the detection of subtle
folding abnormalities. 27 The qualitativescoring system we used, allows for a thorough scoring of brain sulcation
throughout a wide GA range, as it evaluates the primary formation as
well as the presence of secondary and tertiary
sulcation.15 We were not (yet) able to compare our
morphologic findings with postnatal clinical neurobehavioral assessment.
In CDH infants, 9% (4-14%) have abnormal opercularization, which
translates later into language and speech
abnormalities.28 In our study, grading of the
operculum was significantly lower at the first time point as well as at
the second time point, although only left-sided. This may, at least in
theory, have functional consequences: in earlier studies scores using
the same system correlated well with the Neonatal behavioral Assessment
Scale 29, albeit this was in fetuses with isolated
non-severe ventriculomegaly or with late-onset growth restriction. (15,
23) On the other hand, one must take into account that any abnormality
observed postnatally may as well have been acquired after birth.
The significant increase in volume of all fluid compartments at 33 weeks
of gestation in CDH we observed, is in line with work of Radhakishnan et
al. who reported enlarged extra-axial spaces in the third
trimester.8 Because fetuses had normal biometry of the
cerebral hemispheres and lacked major parenchymal abnormalities, the
authors questioned the clinical relevance of these findings.(7) One
other study has reported lower cognitive scores and lesser language
skills in children with larger extra-axial spaces. (6)
Irrespective of the functional impact, what would cause atypical brain
folding as we observed in CDH fetuses, remains unclear. One factor may
be a degree of hemodynamic dysfunction. We have previously reported a
decline in the middle cerebral artery peak systolic velocity, hence in
brain perfusion in fetuses with CDH .5, 30 One may
recognize similarities with circulatory disturbances in fetuses with
congenital heart defects, which coincide with signs of abnormal brain
development. In hypoplastic left heart syndrome (HLHS) a lower blood
flow velocity has been associated with lower brain
volume.31, 32 Furthermore, fetuses with HLHS and other
congenital heart defects display delayed brain maturation in the late
second and early third trimester, and again, this has been linked to
abnormal hemodynamics and oxygen delivery.33 Lucigagni
et al based actually support this theory to explain their recent
findings of altered cortical maturation in CDH newborns.25
Abnormal extra-axial and intraventricular fluid volumes have been
previously explained by a change in cardiac output in CDH caused by
herniation of abdominal structures in turn leading to mild or moderate
cardiac hypoplasia in left-sided CDH.34 Also cardiac
compression may compromise venous return. 2634 This may in turn cause venous congestion and lead
to decreased CSF resorption, 35 and an overall
increase of intracranial fluid. It may be useful to assess cardiac
function and hemodynamics in more detail in fetuses with CDH to study
whether there is a link with brain development.