Preterm brain injury, long-term outcome and brain development study

Very preterm (VPT) birth causes brain injury and affects brain development.
This leads to a broad spectrum of neurodevelopmental disabilities, including
severe motor deficits in 5-10%, and cognitive, behavioural, and socialization
deficits in 25-50% of infants. These problems often first manifest at school
age. At present, our challenge is to detect children at risk of
neurodevelopmental disabilities at an early stage, in order to start early
intervention programs, stimulate development, and minimize the long-term impact
of prematurity.
Magnetic resonance imaging (MRI) enhances the detection of preterm brain injury
and altered brain development. Although neonatal MRI can assist in the
prediction of neurodevelopmental outcome, its prognostic value is still under
debate. Up to now it is not recommended as standard of care for VPT infants. If
MRI proves to predict long-term outcome accurately, it can help to identify
infants at risk of impaired neurodevelopmental outcome. Therefore, long-term
follow-up studies in VPT infants investigated with MRI are essential.
Both preterm birth and brain injury lead to changes in brain volume, maturation
and connectivity in later life that are related to neurodevelopmental
impairments. Reduced cerebral volumes have been reported in childhood and
adolescence in individuals with a history of preterm birth. However,
longitudinal analyses are sparse, and most existing studies do not include
neonatal MRI findings. Therefore, the consequences of nowadays frequently
encountered types of brain injury in preterm infants, such as white matter
injury and cerebellar injury, on subsequent brain development, maturation,
activity and connectivity are still unknown. A longitudinal MRI study that
combines early neonatal MRI findings with childhood neurodevelopmental
follow-up, MRI, and EEG will provide more clarity on the association between
preterm birth, brain injury and subsequent brain development and function. This
is crucial to understand the link between neonatal neuroimaging findings, brain
development and plasticity, and long-term neurodevelopmental outcome.

To investigate the association between preterm brain injury, impaired brain
development and neurodevelopmental outcomes 9-10 years after VPT birth

Non-randomized, single centre, observational cohort study

Follow-up visits are part of routine care for very preterm infants born with a
gestational age <30 weeks, birth weight < 1000 grams, fetal therapy and/or
severe brain injury. Visits are performed according to the guidelines of the
Dutch working party on follow up for preterm infants. Parents and children will
receive a report of the test results and, where necessary, advice for further
support and interventions.
Participating children will not benefit directly from the MRI and EEG
examination. Although, when abnormalities on EEG or MRI are found that require
further treatment, the paediatric neurologist will inform the parents and
advise and treat the infants.
At group level, the results of this study will improve the prediction of
(long-term) neurological prognosis of individual preterm infants and the
understanding of maturational and pathological processes in the brain following
preterm birth. Ultimately this will allow clinicians to provide more informed
prognostic counselling to future parents and anticipatory planning. This can
lead to early and targeted interventions with the potential to prevent
disability and improve outcome.

The risks associated with study participating involving MRI scanning and EEG
are negligible.
The MRI protocol involves a limited number of sequences and takes 20 minutes.
The procedure will be practiced in advance, using a MR simulator. A monitor
will be appointed to monitor the child throughout the MR procedure for verbal
or physical signs of anxiety or resistance. For this purpose a microphone and
camera are present in the MR room. Parents are encouraged to stay with their
children in the MR room. To promote comfort ear protection will be provided
using headphones and music will be offered. If any verbal or physical sign of
resistance is observed by MRI personnel, investigator, monitor or parents the
examination will be interrupted or terminated. No sedatives or anaesthetics
will be used.

EEG examination is performed by experienced staff members to minimize the
duration of registration. During the whole EEG registration parents can stay
with their child. A bed is available for the children during the registration
process to rest on.